diff --git a/404.html b/404.html index 6c324ad..c14e212 100644 --- a/404.html +++ b/404.html @@ -6,16 +6,16 @@ 404 | Bloom Lab - + - +

Whoops, 404

We all make mistakes...

- + \ No newline at end of file diff --git a/README.html b/README.html index 2e14548..4e11304 100644 --- a/README.html +++ b/README.html @@ -6,12 +6,12 @@ Bloom Lab Website | Bloom Lab - + - - - - + + + + @@ -103,8 +103,12 @@ An interactive web tool for visualizing site-level data on a protein structure with the capability of handling complex scenarios like multiple epitopes. ----

Editing the home page and section home pages ​

While the individual posts can be edited by just editing the Markdown, to edit the homepage and the top text for each section (Blog, Team, Papers, Software) you will need to edit the corresponding *.vue file at .vitepress/theme (eg, .vitepress/theme/Home.vue for the home page).

Deployment ​

The deployment is handled by GitHub Actions. A workflow script located at .github/workflows/deploy.yml is run on pushes or pull requests to the main branch. The workflow script builds the website using npm run build and copies the contents of the resulting .dist/ directory to a branch called gh-pages. The website is automatically deployed from the root of this branch by GitHub Pages.

- +---

Editing the home page and section home pages ​

While the individual posts can be edited by just editing the Markdown, to edit the homepage and the top text for each section (Blog, Team, Papers, Software) you will need to edit the corresponding *.vue file at .vitepress/theme (eg, .vitepress/theme/Home.vue for the home page).

However, you can edit the research aims that appear on the Home Page (.vitepress/theme/Home.vue) using markdown files located in research/*.md. These research aims will automatically populate the Home Page.

md
---
+title: Big Datasets and Viral Evolution # Title of the aim
+color: pink # Color  of the underline
+order: 3 # Order of the research aim
+---

The frontmatter above specifies the title of the aim, the color of the title's underline, and the order of the aim.

Deployment ​

The deployment is handled by GitHub Actions. A workflow script located at .github/workflows/deploy.yml is run on pushes or pull requests to the main branch. The workflow script builds the website using npm run build and copies the contents of the resulting .dist/ directory to a branch called gh-pages. The website is automatically deployed from the root of this branch by GitHub Pages.

+ \ No newline at end of file diff --git a/assets/README.md.BlchC57J.lean.js b/assets/README.md.BlchC57J.lean.js deleted file mode 100644 index 4d22f38..0000000 --- a/assets/README.md.BlchC57J.lean.js +++ /dev/null @@ -1 +0,0 @@ -import{_ as s,c as i,o as a,g as e}from"./chunks/framework.BqSDeblO.js";const E=JSON.parse('{"title":"Bloom Lab Website","description":"","frontmatter":{},"headers":[],"relativePath":"README.md","filePath":"README.md"}'),t={name:"README.md"},n=e("",59),l=[n];function h(p,o,d,k,r,c){return a(),i("div",null,l)}const y=s(t,[["render",h]]);export{E as __pageData,y as default}; diff --git a/assets/README.md.BlchC57J.js b/assets/README.md.D8eBG4ob.js similarity index 94% rename from assets/README.md.BlchC57J.js rename to assets/README.md.D8eBG4ob.js index ad997eb..1327a6d 100644 --- a/assets/README.md.BlchC57J.js +++ b/assets/README.md.D8eBG4ob.js @@ -1,4 +1,4 @@ -import{_ as s,c as i,o as a,g as e}from"./chunks/framework.BqSDeblO.js";const E=JSON.parse('{"title":"Bloom Lab Website","description":"","frontmatter":{},"headers":[],"relativePath":"README.md","filePath":"README.md"}'),t={name:"README.md"},n=e(`

Bloom Lab Website ​

This repository contains the code the Bloom Lab's public website. The website is based on a custom VitePress theme. Using VitePress allows us to take advantage of the VitePress ecosystem for routing and markdown processing.

Contributions to the website are made by writing markdown documents and editing YAML and JSON configuration files.

The content of our lab's website draws inspiration from lab websites like those of Trevor Bedford, Erick Matsen, and Michael Elowitz. We also borrow styles from VitePress to maintain consistency with our other VitePress websites.

Installation ​

Contributions to the lab website are made through GitHub using pull requests.

Clone the git repository locally to edit the site:

bash
git clone https://github.com/jbloomlab/jbloomlab.github.io
+import{_ as s,c as i,o as a,g as e}from"./chunks/framework.D4bY2S_W.js";const E=JSON.parse('{"title":"Bloom Lab Website","description":"","frontmatter":{},"headers":[],"relativePath":"README.md","filePath":"README.md"}'),t={name:"README.md"},n=e(`
Bloom Lab Website ​
This repository contains the code the Bloom Lab's public website. The website is based on a custom VitePress theme. Using VitePress allows us to take advantage of the VitePress ecosystem for routing and markdown processing.
Contributions to the website are made by writing markdown documents and editing YAML and JSON configuration files.
The content of our lab's website draws inspiration from lab websites like those of Trevor Bedford, Erick Matsen, and Michael Elowitz. We also borrow styles from VitePress to maintain consistency with our other VitePress websites.
Installation ​
Contributions to the lab website are made through GitHub using pull requests.
Clone the git repository locally to edit the site:
bash
git clone https://github.com/jbloomlab/jbloomlab.github.io
 cd jbloomlab.github.io
You'll need to install Javascript and its relevant packages to preview the site as you make changes. You're going to need two pieces of software to do this: Node.js and npm.
Node.js is an environment that allows you to run Javascript code on your computer. npm is a package manager that contains the Javascript libraries necessary to create the website. The instructions for installing Node and npm depend on your operating system and personal preference.
Without conda ​
Follow the instructions here to install Node without a package manager.
With conda ​
If you have conda on your operating system, you can use it to install node and npm.
bash
conda env create -f environment.yml
 conda activate jbloomlab.org
Install npm packages and view page ​
Regardless of how you installed Node and npm, verify that the installation worked by running:
bash
node -v
 npm -v
If this is the first time you're contributing to the website, you'll need to tell npm to install all of the packages in the package.json file. To do this, run the following command from within the repository:
bash
npm install
Developing ​
While you're editing the content of the website, it's important to see a live preview of your changes. You can do this by booting up a local "development" server to open the local version of the lab website on your browser. To do this, simply run:
bash
npm run dev
Now, there will be a local version of the website running at http://localhost:5173 (or some other URL printed to the console). Visit this URL in your browser to see a preview of the site.
Contributing ​
The general file structure of this website is as follows:
bash
.
@@ -84,4 +84,8 @@ import{_ as s,c as i,o as a,g as e}from"./chunks/framework.BqSDeblO.js";const E=
 
 An interactive web tool for visualizing site-level data on a protein structure with the capability of handling complex scenarios like multiple epitopes.
 
----
Editing the home page and section home pages ​
While the individual posts can be edited by just editing the Markdown, to edit the homepage and the top text for each section (Blog, Team, Papers, Software) you will need to edit the corresponding *.vue file at .vitepress/theme (eg, .vitepress/theme/Home.vue for the home page).
Deployment ​
The deployment is handled by GitHub Actions. A workflow script located at .github/workflows/deploy.yml is run on pushes or pull requests to the main branch. The workflow script builds the website using npm run build and copies the contents of the resulting .dist/ directory to a branch called gh-pages. The website is automatically deployed from the root of this branch by GitHub Pages.
`,59),l=[n];function h(p,o,d,k,r,c){return a(),i("div",null,l)}const y=s(t,[["render",h]]);export{E as __pageData,y as default};
+---

Editing the home page and section home pages ​

While the individual posts can be edited by just editing the Markdown, to edit the homepage and the top text for each section (Blog, Team, Papers, Software) you will need to edit the corresponding *.vue file at .vitepress/theme (eg, .vitepress/theme/Home.vue for the home page).

However, you can edit the research aims that appear on the Home Page (.vitepress/theme/Home.vue) using markdown files located in research/*.md. These research aims will automatically populate the Home Page.

md
---
+title: Big Datasets and Viral Evolution # Title of the aim
+color: pink # Color  of the underline
+order: 3 # Order of the research aim
+---

The frontmatter above specifies the title of the aim, the color of the title's underline, and the order of the aim.

Deployment ​

The deployment is handled by GitHub Actions. A workflow script located at .github/workflows/deploy.yml is run on pushes or pull requests to the main branch. The workflow script builds the website using npm run build and copies the contents of the resulting .dist/ directory to a branch called gh-pages. The website is automatically deployed from the root of this branch by GitHub Pages.

`,62),l=[n];function h(p,o,d,k,r,c){return a(),i("div",null,l)}const y=s(t,[["render",h]]);export{E as __pageData,y as default}; diff --git a/assets/README.md.D8eBG4ob.lean.js b/assets/README.md.D8eBG4ob.lean.js new file mode 100644 index 0000000..015fe71 --- /dev/null +++ b/assets/README.md.D8eBG4ob.lean.js @@ -0,0 +1 @@ +import{_ as s,c as i,o as a,g as e}from"./chunks/framework.D4bY2S_W.js";const E=JSON.parse('{"title":"Bloom Lab Website","description":"","frontmatter":{},"headers":[],"relativePath":"README.md","filePath":"README.md"}'),t={name:"README.md"},n=e("",62),l=[n];function h(p,o,d,k,r,c){return a(),i("div",null,l)}const y=s(t,[["render",h]]);export{E as __pageData,y as default}; diff --git a/assets/app.BT9Bm16P.js b/assets/app.CcfNRZmG.js similarity index 64% rename from assets/app.BT9Bm16P.js rename to assets/app.CcfNRZmG.js index 439a3a7..b21864d 100644 --- a/assets/app.BT9Bm16P.js +++ b/assets/app.CcfNRZmG.js @@ -1 +1 @@ -import{V as o,W as p,X as u,Y as l,Z as c,$ as f,a0 as d,a1 as m,a2 as h,a3 as A,a4 as g,a5 as P,a6 as _,u as v,D as R,a7 as w,a8 as y,a9 as C,aa as E,ab as b}from"./chunks/framework.BqSDeblO.js";import{R as T}from"./chunks/theme.BYdNhcMK.js";function i(e){if(e.extends){const a=i(e.extends);return{...a,...e,async enhanceApp(t){a.enhanceApp&&await a.enhanceApp(t),e.enhanceApp&&await e.enhanceApp(t)}}}return e}const s=i(T),D=_({name:"VitePressApp",setup(){const{site:e,lang:a,dir:t}=v();return R(()=>{w(()=>{document.documentElement.lang=a.value,document.documentElement.dir=t.value})}),e.value.router.prefetchLinks&&y(),C(),E(),s.setup&&s.setup(),()=>b(s.Layout)}});async function S(){globalThis.__VITEPRESS__=!0;const e=L(),a=V();a.provide(u,e);const t=l(e.route);return a.provide(c,t),a.component("Content",f),a.component("ClientOnly",d),Object.defineProperties(a.config.globalProperties,{$frontmatter:{get(){return t.frontmatter.value}},$params:{get(){return t.page.value.params}}}),s.enhanceApp&&await s.enhanceApp({app:a,router:e,siteData:m}),{app:a,router:e,data:t}}function V(){return h(D)}function L(){let e=o,a;return A(t=>{let n=g(t),r=null;return n&&(e&&(a=n),(e||a===n)&&(n=n.replace(/\.js$/,".lean.js")),r=P(()=>import(n),[])),o&&(e=!1),r},s.NotFound)}o&&S().then(({app:e,router:a,data:t})=>{a.go().then(()=>{p(a.route,t.site),e.mount("#app")})});export{S as createApp}; +import{V as o,W as p,X as u,Y as l,Z as c,$ as f,a0 as d,a1 as m,a2 as h,a3 as A,a4 as g,a5 as P,a6 as _,u as v,B as R,a7 as w,a8 as y,a9 as C,aa as E,ab as b}from"./chunks/framework.D4bY2S_W.js";import{R as T}from"./chunks/theme.DwK3Lct_.js";function i(e){if(e.extends){const a=i(e.extends);return{...a,...e,async enhanceApp(t){a.enhanceApp&&await a.enhanceApp(t),e.enhanceApp&&await e.enhanceApp(t)}}}return e}const s=i(T),S=_({name:"VitePressApp",setup(){const{site:e,lang:a,dir:t}=v();return R(()=>{w(()=>{document.documentElement.lang=a.value,document.documentElement.dir=t.value})}),e.value.router.prefetchLinks&&y(),C(),E(),s.setup&&s.setup(),()=>b(s.Layout)}});async function D(){globalThis.__VITEPRESS__=!0;const e=L(),a=V();a.provide(u,e);const t=l(e.route);return a.provide(c,t),a.component("Content",f),a.component("ClientOnly",d),Object.defineProperties(a.config.globalProperties,{$frontmatter:{get(){return t.frontmatter.value}},$params:{get(){return t.page.value.params}}}),s.enhanceApp&&await s.enhanceApp({app:a,router:e,siteData:m}),{app:a,router:e,data:t}}function V(){return h(S)}function L(){let e=o,a;return A(t=>{let n=g(t),r=null;return n&&(e&&(a=n),(e||a===n)&&(n=n.replace(/\.js$/,".lean.js")),r=P(()=>import(n),[])),o&&(e=!1),r},s.NotFound)}o&&D().then(({app:e,router:a,data:t})=>{a.go().then(()=>{p(a.route,t.site),e.mount("#app")})});export{D as createApp}; diff --git a/assets/chunks/framework.BqSDeblO.js b/assets/chunks/framework.D4bY2S_W.js similarity index 98% 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In the Bloom lab, we study the evolution of viruses and proteins. We use experimental and computational techniques to understand the molecular constraints on viral proteins, and how these constraints shape the capacity of viruses to evolve to escape antibodies, erode pre-existing immunity, and adapt to new hosts.

Our lab is part of the Basic Sciences Divison and the Computational Biology Program at the Fred Hutch. We are also affiliated with the Genome Sciences and Microbiology Departments at the University of Washington, and graduate students often join our lab through the MCB program. Jesse Bloom is an Investigator of the Howard Hughes Medical Institute.

',1),tr={class:"scroll-button pb-60 sm:pb-72 md:pb-72 lg:pb-60"},or={key:0},rr=se(()=>f("p",{class:"text-sm md:text-base lg:text-lg text-gray-500 mt-10 md:mt-6 lg:mt-12 text-center"}," Scroll down to learn more ",-1)),nr=se(()=>f("div",{class:"flex justify-center"},[f("i",{class:"bi bi-chevron-down text-gray-500 mt-1 animate-bounce text-lg md:text-xl lg:text-2xl"})],-1)),ar=[rr,nr],ir={class:"carousel-item w-full h-full snap-always snap-start mx-auto max-w-4xl px-4 text-left flex flex-col justify-between"},sr=He('

Deep Mutational Scanning

Our lab uses deep mutational scanning to experimentally measure how tens-of-thousands of mutations to viral proteins affect key properties including function, immune escape, and receptor binding.

Example of deep mutational scanning

We primarily perform these experiments using a pseudovirus system that allows us to safely characterize mutants of entry proteins from a wide range of viruses, including SARS-CoV-2 spike, influenza hemagglutinin, Lassa virus GPC, HIV envelope, and Nipah virus RBP.

Deep mutational scanning can inform efforts to forecast the evolution of human seasonal viruses and surveil the evolution of potential pandemic viruses. To facilitate the use of deep mutational scanning for these important goals, we develop interactive visualization tools and data analysis pipelines. See here for an example of how we analyze and visualize large datasets to inform the study of viral evolution.

',1),lr={class:"scroll-button pb-60 sm:pb-72 md:pb-72 lg:pb-60"},cr={key:0},dr=se(()=>f("p",{class:"text-sm md:text-base lg:text-lg text-gray-500 mt-10 md:mt-6 lg:mt-12 text-center"}," Scroll down to learn more ",-1)),ur=se(()=>f("div",{class:"flex justify-center"},[f("i",{class:"bi bi-chevron-down text-gray-500 mt-1 animate-bounce text-lg md:text-xl lg:text-2xl"})],-1)),fr=[dr,ur],pr={class:"carousel-item w-full h-full snap-always snap-start mx-auto max-w-4xl px-4 text-left flex flex-col justify-between"},mr=He('

Interplay of Immunity and Viral Evolution

We study immunity and viral evolution at both the population and single-cell levels.

Description

At the population level, differences in exposure history and immune imprinting lead human individuals to make antibody responses that target different regions of rapidly evolving viruses like influenza and SARS-CoV-2. This population heterogeneity has profound implications for viral evolution and disease susceptibility, as it causes viral mutations to impact the immunity of different individuals differently. We are characterizing this population heterogeneity using both deep mutational scanning and a sequencing based-neutralization assay we developed that increases the throughput of traditional neutralization assays by several orders of magnitude (see schematic at left).

At the single-cell level, we developed approaches to sequence viruses in single cells and quantify how many progeny each infected cell produces. We use these approaches to understand how viral variation impacts the outcome of infection in individual cells.

',1),hr={class:"scroll-button pb-60 sm:pb-72 md:pb-72 lg:pb-60"},gr={key:0},br=se(()=>f("p",{class:"text-sm md:text-base lg:text-lg text-gray-500 mt-10 md:mt-6 lg:mt-12 text-center"}," Scroll down to learn more ",-1)),vr=se(()=>f("div",{class:"flex justify-center"},[f("i",{class:"bi bi-chevron-down text-gray-500 mt-1 animate-bounce text-lg md:text-xl lg:text-2xl"})],-1)),yr=[br,vr],kr={class:"carousel-item w-full h-full snap-always snap-start mx-auto max-w-4xl px-4 text-left flex flex-col justify-between"},xr=He('

Big Datasets and Viral Evolution

We also develop new ways to leverage large datasets to better understand viral evolution.

We have come up with a way to leverage the millions of publicly available SARS-CoV-2 sequences to estimate the effect of individual mutations on viral fitness (see this paper and these slides). We've also created a platform to visualize the mutational effects to aid in interpretation of viral evolution.

We have also integrated thousands of deep mutational scanning measurements into an antibody-escape calculator that was widely used during the SARS-CoV-2 pandemic to understand the antigenic effects of viral mutations.

We also have projects that involve analyzing the evolution of viruses within individual infected humans, and developing models to understand epistasis among viral mutations.

',1),wr={class:"scroll-button pb-60 sm:pb-72 md:pb-72 lg:pb-60"},Sr={key:0},Cr=se(()=>f("p",{class:"text-sm md:text-base lg:text-lg text-gray-500 mt-10 md:mt-6 lg:mt-12 text-center"}," Scroll up to learn more ",-1)),_r=se(()=>f("div",{class:"flex justify-center"},[f("i",{class:"bi bi-chevron-up text-gray-500 mt-1 animate-bounce text-lg md:text-xl lg:text-2xl"})],-1)),Br=[Cr,_r];function Or(o,e,t,r,n,a){return m(),y("div",qo,[f("div",Yo,[f("div",Zo,[Xo,f("p",Qo,[ee(" where we study the evolution of "),H(he,{name:"fade",mode:"out-in"},{default:Y(()=>[(m(),y("span",{key:n.currentVirus,class:"italic",style:Co({color:n.currentColor,backgroundColor:a.getBackgroundWithOpacity(n.currentColor)})},j(n.currentVirus),5))]),_:1})]),er]),f("div",tr,[H(he,null,{default:Y(()=>[n.show?(m(),y("div",or,ar)):P("",!0)]),_:1})])]),f("div",ir,[sr,f("div",lr,[H(he,null,{default:Y(()=>[n.show?(m(),y("div",cr,fr)):P("",!0)]),_:1})])]),f("div",pr,[mr,f("div",hr,[H(he,null,{default:Y(()=>[n.show?(m(),y("div",gr,yr)):P("",!0)]),_:1})])]),f("div",kr,[xr,f("div",wr,[H(he,null,{default:Y(()=>[n.show?(m(),y("div",Sr,Br)):P("",!0)]),_:1})])])])}const $r=J(Uo,[["render",Or],["__scopeId","data-v-3f9973aa"]]),Ir={props:{date:String},methods:{getFormattedDate(){const o={year:"numeric",month:"long",day:"numeric"};return new Date(this.date).toLocaleDateString("en-US",o)}}},Ar=f("dt",{class:"sr-only"},"Published on",-1),jr={class:"text-base leading-6 font-medium text-gray-500"},Tr=["datetime"];function Pr(o,e,t,r,n,a){return m(),y("dl",null,[Ar,f("dd",jr,[f("time",{datetime:a.getFormattedDate()},j(a.getFormattedDate()),9,Tr)])])}const Lr=J(Ir,[["render",Pr]]),Rr=JSON.parse('[{"title":"Deep mutational scanning of H5 influenza hemagglutinin","author":"Jesse Bloom","date":"2024-05-25T00:00:00.000Z","excerpt":"

In a new study, we have measured how all mutations to the hemagglutinin (HA) of clade 2.3.4.4b H5 influenza affect molecular phenotypes relevant to pandemic risk.\\nThe data can be interactively visualized at https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/

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")],-1),zr={class:"divide-y divide-gray-200"},Mr={class:"space-y-2 xl:grid xl:grid-cols-4 xl:space-y-0 xl:items-baseline"},Fr={class:"space-y-5 xl:col-span-3"},Nr={class:"space-y-6"},Hr={class:"text-2xl leading-8 font-bold tracking-tight"},Wr=["href"],Kr=["innerHTML"],Jr={class:"text-base leading-6 font-medium"},Gr=["href"];function Ur(o,e,t,r,n,a){const s=K("Date");return m(),y("div",Vr,[Er,f("ul",zr,[(m(!0),y(W,null,Z(n.posts,i=>(m(),y("li",{class:"py-12",key:i.url},[f("article",Mr,[H(s,{date:i.date},null,8,["date"]),f("div",Fr,[f("div",Nr,[f("h2",Hr,[f("a",{class:"text-gray-900 hover:text-gray-900 no-underline",href:i.url},j(i.title),9,Wr)]),i.excerpt?(m(),y("div",{key:0,class:"max-w-none text-gray-500",innerHTML:i.excerpt},null,8,Kr)):P("",!0)]),f("div",Jr,[f("a",{class:"text-custom-orange no-underline","aria-label":"read more about {{ post.title }}",href:i.url},"Read more →",8,Gr)])])])]))),128))])])}const qr=J(Dr,[["render",Ur]]),Yr=JSON.parse('[{"name":"Andrea 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Python package to parse complex user-defined features from long-read PacBio sequencing.

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Snakemake pipeline for analyzing deep mutational scanning of barcoded viral entry proteins.

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Interactive web tool for visualizing mutation data on a protein structure.

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Python package for fitting neutralization curves.

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Python package for modeling mutational escape from polyclonal antibodies using deep mutational scanning data.

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Snakemake pipeline for analyzing sequencing-based neutralization assays.

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Software

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We also develop new ways to leverage large datasets to better understand viral evolution.

\\n

We have come up with a way to leverage the millions of publicly available SARS-CoV-2 sequences to estimate the effect of individual mutations on viral fitness (see this paper and these slides). We've also created a platform to visualize the mutational effects to aid in interpretation of viral evolution.

\\n

We have also integrated thousands of deep mutational scanning measurements into an antibody-escape calculator that was widely used during the SARS-CoV-2 pandemic to understand the antigenic effects of viral mutations.

\\n

We also have projects that involve analyzing the evolution of viruses within individual infected humans, and developing models to understand epistasis among viral mutations.

\\n"},{"title":"Deep Mutational Scanning","color":"sky","order":1,"html":"

Our lab uses deep mutational scanning to experimentally measure how tens-of-thousands of mutations to viral proteins affect key properties including function, immune escape, and receptor binding.

\\n

\\""Pseudovirus

\\n

We primarily perform these experiments using a pseudovirus system that allows us to safely characterize mutants of entry proteins from a wide range of viruses, including SARS-CoV-2 spike, influenza hemagglutinin, Lassa virus GPC, HIV envelope, and Nipah virus RBP.

\\n

Deep mutational scanning can inform efforts to forecast the evolution of human seasonal viruses and surveil the evolution of potential pandemic viruses. To facilitate the use of deep mutational scanning for these important goals, we develop interactive visualization tools and data analysis pipelines. See here for an example of how we analyze and visualize large datasets to inform the study of viral evolution.

\\n"},{"title":"Interplay of Immunity and Viral Evolution","color":"indigo","order":2,"html":"

We study immunity and viral evolution at both the population and single-cell levels.

\\n

\\""Sequencing-based

\\n

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\\n

At the single-cell level, we developed approaches to sequence viruses in single cells and quantify how many progeny each infected cell produces. We use these approaches to understand how viral variation impacts the outcome of infection in individual cells.

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In the Bloom lab, we study the evolution of viruses and proteins. We use experimental and computational techniques to understand the molecular constraints on viral proteins, and how these constraints shape the capacity of viruses to evolve to escape antibodies, erode pre-existing immunity, and adapt to new hosts.

Our lab is part of the Basic Sciences Divison and the Computational Biology Program at the Fred Hutch. We are also affiliated with the Genome Sciences and Microbiology Departments at the University of Washington, and graduate students often join our lab through the MCB program. Jesse Bloom is an Investigator of the Howard Hughes Medical Institute.

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scanning","Immunity"],"url":"/papers/2019_lee.html"},{"title":"Single-cell virus sequencing of influenza infections that trigger innate immunity","date":"2019-07-15","authors":["Alistair B Russell","Elizaveta Elshina","Jacob R Kowalsky","Aartjan JW Te Velthuis","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.00500-19","link":"https://journals.asm.org/doi/full/10.1128/jvi.00500-19","image":"/assets/papers/2019_russell.jpg","keywords":["Influenza","Single-cell sequencing"],"url":"/papers/2019_russell.html"},{"title":"Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide","date":"2019-05-15","authors":["Adam S Dingens","Dana Arenz","Julie Overbaugh","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v11050439","link":"https://www.mdpi.com/1999-4915/11/5/439","image":"/assets/papers/2019_dingens_a.jpg","keywords":["HIV","Deep mutational scanning"],"url":"/papers/2019_dingens_a.html"},{"title":"Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans","date":"2019-04-30","authors":["YQ Shirleen Soh","Louise H Moncla","Rachel Eguia","Trevor Bedford","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.45079","link":"https://doi.org/10.7554/eLife.45079","image":"/assets/papers/2019_soh.jpg","keywords":["Influenza","Deep mutational scanning"],"url":"/papers/2019_soh.html"},{"title":"An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes","date":"2019-02-19","authors":["Adam S Dingens","Dana Arenz","Haidyn Weight","Julie Overbaugh","Jesse D Bloom"],"journal":"Immunity","doi":"10.1016/j.immuni.2018.12.017","link":"https://www.sciencedirect.com/science/article/pii/S107476131830565X?via%3Dihub","image":"/assets/papers/2019_dingens_b.jpg","keywords":["HIV","Deep mutational scanning"],"url":"/papers/2019_dingens_b.html"},{"title":"alignparse: A Python package for parsing complex features from high-throughput long-read sequencing","date":"2019-01-23","authors":["Katharine HD Crawford","Jesse D Bloom"],"journal":"JOSS","doi":"10.21105/joss.01915","link":"https://doi.org/10.21105%2Fjoss.01915","image":"/assets/papers/2019_crawford.png","keywords":["Software tools"],"url":"/papers/2019_crawford.html"},{"title":"Comprehensive profiling of translation initiation in influenza virus infected cells","date":"2019-01-23","authors":["Heather M Machkovech","Jesse D Bloom","Arvind R Subramaniam"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1007518","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007518","image":"/assets/papers/2019_machkovech.png","keywords":["Influenza"],"url":"/papers/2019_machkovech.html"},{"title":"Within-host evolution of human influenza virus","date":"2018-09-01","authors":["Katherine S Xue","Louise H Moncla","Trevor Bedford","Jesse D Bloom"],"journal":"Trends in Microbiology","doi":"10.1016/j.tim.2018.02.007","link":"https://www.cell.com/trends/microbiology/fulltext/S0966-842X(18)30043-X","image":"/assets/papers/2018_xue_a.jpg","keywords":["Influenza","Within-host evolution"],"url":"/papers/2018_xue_a.html"},{"title":"Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants","date":"2018-08-28","authors":["Juhye M Lee","John Huddleston","Michael B Doud","Kathryn A Hooper","Nicholas C Wu","Trevor Bedford","Jesse D Bloom"],"journal":"PNAS","doi":"10.1073/pnas.1806133115","link":"https://www.pnas.org/doi/abs/10.1073/pnas.1806133115","image":"/assets/papers/2018_lee.jpg","keywords":["Influenza","Deep mutational scanning"],"url":"/papers/2018_lee.html"},{"title":"Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV","date":"2018-07-05","authors":["Adam S Dingens","Priyamvada Acharya","Hugh K Haddox","Reda Rawi","Kai Xu","Gwo-Yu Chuang","Hui Wei","Baoshan Zhang","John R Mascola","Bridget Carragher","Clinton S Potter","Julie Overbaugh","Peter D Kwong","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1007159","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007159","image":"/assets/papers/2018_dingens.png","keywords":["HIV","Deep mutational scanning"],"url":"/papers/2018_dingens.html"},{"title":"Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence","date":"2018-07-01","authors":["Sarah K Hilton","Jesse D Bloom"],"journal":"Virus evolution","doi":"10.1093/ve/vey033","link":"https://academic.oup.com/ve/article/4/2/vey033/5163287","image":"/assets/papers/2018_hilton.jpg","keywords":["Phylogenetics"],"url":"/papers/2018_hilton.html"},{"title":"How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin","date":"2018-04-11","authors":["Michael B Doud*","Juhye M Lee*","Jesse D Bloom"],"journal":"Nature communications","doi":"10.1038/s41467-018-03665-3","link":"https://www.nature.com/articles/s41467-018-03665-3","image":"/assets/papers/2018_doud.jpg","keywords":["Influenza","Deep mutational scanning"],"url":"/papers/2018_doud.html"},{"title":"Mapping mutational effects along the evolutionary landscape of HIV envelope","date":"2018-03-28","authors":["Hugh K Haddox*","Adam S Dingens*","Sarah K Hilton","Julie Overbaugh","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.34420","link":"https://elifesciences.org/articles/34420","image":"/assets/papers/2018_haddox.jpg","keywords":["HIV","Deep mutational scanning","Epistasis"],"url":"/papers/2018_haddox.html"},{"title":"Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples","date":"2018-02-28","authors":["Katherine S Xue","Alexander L Greninger","Ailyn Pérez-Osorio","Jesse D Bloom"],"journal":"MSphere","doi":"10.1128/mspheredirect.00552-17","link":"https://journals.asm.org/doi/full/10.1128/mspheredirect.00552-17","image":"/assets/papers/2018_xue_b.jpg","keywords":["Influenza","Within-host evolution"],"url":"/papers/2018_xue_b.html"},{"title":"Extreme heterogeneity of influenza virus infection in single cells","date":"2018-02-16","authors":["Alistair B Russell","Cole Trapnell","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.32303","link":"https://elifesciences.org/articles/32303","image":"/assets/papers/2018_russell.jpg","keywords":["Influenza","Single-cell sequencing"],"url":"/papers/2018_russell.html"},{"title":"Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models","date":"2017-12-01","authors":["Jesse D Bloom"],"journal":"Biology 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Bloom"],"journal":"eLife","doi":"10.7554/eLife.26875.001","link":"https://elifesciences.org/articles/26875","image":"/assets/papers/2017_xue.jpg","keywords":["Influenza","Within-host evolution"],"url":"/papers/2017_xue.html"},{"title":"Comprehensive mapping of HIV-1 escape from a broadly neutralizing antibody","date":"2017-06-14","authors":["Adam S Dingens","Hugh K Haddox","Julie Overbaugh","Jesse D Bloom"],"journal":"Cell host & microbe","doi":"10.1016/j.chom.2017.05.003","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(17)30196-8.pdf","image":"/assets/papers/2017_dingens.jpg","keywords":["HIV","Deep mutational scanning"],"url":"/papers/2017_dingens.html"},{"title":"Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA","date":"2017-03-27","authors":["Orr Ashenberg","Jai Padmakumar","Michael B Doud","Jesse D Bloom"],"journal":"PLoS 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Python package to parse complex user-defined features from long-read PacBio sequencing.

\\n","url":"/projects/alignparse.html"},{"name":"dms-vep-pipeline-3","github":"https://github.com/dms-vep/dms-vep-pipeline-3","documentation":"https://github.com/dms-vep/dms-vep-pipeline-3","link":"https://github.com/dms-vep/dms-vep-pipeline-3","excerpt":"

Snakemake pipeline for analyzing deep mutational scanning of barcoded viral entry proteins.

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Interactive web tool for visualizing mutation data on a protein structure.

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Python package for fitting neutralization curves.

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Python package for modeling mutational escape from polyclonal antibodies using deep mutational scanning data.

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Snakemake pipeline for analyzing sequencing-based neutralization assays.

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Software

Below are some of the main software packages maintained by our lab. For a complete list of projects, check out the https://github.com/jbloomlab (most lab projects) and https://github.com/dms-vep (projects related to deep mutational scanning of viral entry proteins).

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t=(this.items||[]).length,r=this.isBoth()?this.first.rows+e:this.first+e;return{index:r,count:t,first:r===0,last:r===t-1,even:r%2===0,odd:r%2!==0}},getLoaderOptions:function(e,t){var r=this.loaderArr.length;return Se({index:e,count:r,first:e===0,last:e===r-1,even:e%2===0,odd:e%2!==0},t)},getPageByFirst:function(e){return Math.floor(((e??this.first)+this.d_numToleratedItems*4)/(this.step||1))},isPageChanged:function(e){return this.step?this.page!==this.getPageByFirst(e??this.first):!0},setContentEl:function(e){this.content=e||this.content||B.findSingle(this.element,'[data-pc-section="content"]')},elementRef:function(e){this.element=e},contentRef:function(e){this.content=e}},computed:{containerClass:function(){return["p-virtualscroller",this.class,{"p-virtualscroller-inline":this.inline,"p-virtualscroller-both p-both-scroll":this.isBoth(),"p-virtualscroller-horizontal 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t=e.instance,r=e.props;return["p-multiselect-label",{"p-placeholder":t.label===r.placeholder,"p-multiselect-label-empty":!r.placeholder&&(!r.modelValue||r.modelValue.length===0)}]},chipItem:"p-multiselect-chip-item",pcChip:"p-multiselect-chip",chipIcon:"p-multiselect-chip-icon",dropdown:"p-multiselect-dropdown",loadingIcon:"p-multiselect-loading-icon",dropdownIcon:"p-multiselect-dropdown-icon",overlay:"p-multiselect-overlay p-component",header:"p-multiselect-header",pcFilterContainer:"p-multiselect-filter-container",pcFilter:"p-multiselect-filter",listContainer:"p-multiselect-list-container",list:"p-multiselect-list",optionGroup:"p-multiselect-option-group",option:function(e){var 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t=e.target.value;this.filterValue=t,this.focusedOptionIndex=-1,this.$emit("filter",{originalEvent:e,value:t}),!this.virtualScrollerDisabled&&this.virtualScroller.scrollToIndex(0)},onFilterKeyDown:function(e){switch(e.code){case"ArrowDown":this.onArrowDownKey(e);break;case"ArrowUp":this.onArrowUpKey(e,!0);break;case"ArrowLeft":case"ArrowRight":this.onArrowLeftKey(e,!0);break;case"Home":this.onHomeKey(e,!0);break;case"End":this.onEndKey(e,!0);break;case"Enter":case"NumpadEnter":this.onEnterKey(e);break;case"Escape":this.onEscapeKey(e);break;case"Tab":this.onTabKey(e,!0);break}},onFilterBlur:function(){this.focusedOptionIndex=-1},onFilterUpdated:function(){this.overlayVisible&&this.alignOverlay()},onOverlayClick:function(e){Oc.emit("overlay-click",{originalEvent:e,target:this.$el})},onOverlayKeyDown:function(e){switch(e.code){case"Escape":this.onEscapeKey(e);break}},onArrowDownKey:function(e){if(!this.overlayVisible)this.show();else{var t=this.focusedOptionIndex!==-1?this.findNextOptionIndex(this.focusedOptionIndex):this.clicked?this.findFirstOptionIndex():this.findFirstFocusedOptionIndex();e.shiftKey&&this.onOptionSelectRange(e,this.startRangeIndex,t),this.changeFocusedOptionIndex(e,t)}e.preventDefault()},onArrowUpKey:function(e){var t=arguments.length>1&&arguments[1]!==void 0?arguments[1]:!1;if(e.altKey&&!t)this.focusedOptionIndex!==-1&&this.onOptionSelect(e,this.visibleOptions[this.focusedOptionIndex]),this.overlayVisible&&this.hide(),e.preventDefault();else{var r=this.focusedOptionIndex!==-1?this.findPrevOptionIndex(this.focusedOptionIndex):this.clicked?this.findLastOptionIndex():this.findLastFocusedOptionIndex();e.shiftKey&&this.onOptionSelectRange(e,r,this.startRangeIndex),this.changeFocusedOptionIndex(e,r),!this.overlayVisible&&this.show(),e.preventDefault()}},onArrowLeftKey:function(e){var t=arguments.length>1&&arguments[1]!==void 0?arguments[1]:!1;t&&(this.focusedOptionIndex=-1)},onHomeKey:function(e){var 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a=e.metaKey||e.ctrlKey,s=this.findLastOptionIndex();e.shiftKey&&a&&this.onOptionSelectRange(e,this.startRangeIndex,s),this.changeFocusedOptionIndex(e,s),!this.overlayVisible&&this.show()}e.preventDefault()},onPageUpKey:function(e){this.scrollInView(0),e.preventDefault()},onPageDownKey:function(e){this.scrollInView(this.visibleOptions.length-1),e.preventDefault()},onEnterKey:function(e){this.overlayVisible?this.focusedOptionIndex!==-1&&(e.shiftKey?this.onOptionSelectRange(e,this.focusedOptionIndex):this.onOptionSelect(e,this.visibleOptions[this.focusedOptionIndex])):(this.focusedOptionIndex=-1,this.onArrowDownKey(e)),e.preventDefault()},onEscapeKey:function(e){this.overlayVisible&&this.hide(!0),e.preventDefault()},onTabKey:function(e){var t=arguments.length>1&&arguments[1]!==void 0?arguments[1]:!1;t||(this.overlayVisible&&this.hasFocusableElements()?(B.focus(e.shiftKey?this.$refs.lastHiddenFocusableElementOnOverlay:this.$refs.firstHiddenFocusableElementOnOverlay),e.preventDefault()):(this.focusedOptionIndex!==-1&&this.onOptionSelect(e,this.visibleOptions[this.focusedOptionIndex]),this.overlayVisible&&this.hide(this.filter)))},onShiftKey:function(){this.startRangeIndex=this.focusedOptionIndex},onOverlayEnter:function(e){nt.set("overlay",e,this.$primevue.config.zIndex.overlay),B.addStyles(e,{position:"absolute",top:"0",left:"0"}),this.alignOverlay(),this.scrollInView(),this.autoFilterFocus&&B.focus(this.$refs.filterInput.$el)},onOverlayAfterEnter:function(){this.bindOutsideClickListener(),this.bindScrollListener(),this.bindResizeListener(),this.$emit("show")},onOverlayLeave:function(){this.unbindOutsideClickListener(),this.unbindScrollListener(),this.unbindResizeListener(),this.$emit("hide"),this.overlay=null},onOverlayAfterLeave:function(e){nt.clear(e)},alignOverlay:function(){this.appendTo==="self"?B.relativePosition(this.overlay,this.$el):(this.overlay.style.minWidth=B.getOuterWidth(this.$el)+"px",B.absolutePosition(this.overlay,this.$el))},bindOutsideClickListener:function(){var e=this;this.outsideClickListener||(this.outsideClickListener=function(t){e.overlayVisible&&e.isOutsideClicked(t)&&e.hide()},document.addEventListener("click",this.outsideClickListener))},unbindOutsideClickListener:function(){this.outsideClickListener&&(document.removeEventListener("click",this.outsideClickListener),this.outsideClickListener=null)},bindScrollListener:function(){var e=this;this.scrollHandler||(this.scrollHandler=new As(this.$refs.container,function(){e.overlayVisible&&e.hide()})),this.scrollHandler.bindScrollListener()},unbindScrollListener:function(){this.scrollHandler&&this.scrollHandler.unbindScrollListener()},bindResizeListener:function(){var 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t=this;if(this.selectAll!==null)this.$emit("selectall-change",{originalEvent:e,checked:!this.allSelected});else{var r=this.allSelected?[]:this.visibleOptions.filter(function(n){return t.isValidOption(n)}).map(function(n){return t.getOptionValue(n)});this.updateModel(e,r)}},removeOption:function(e,t){var r=this;e.stopPropagation();var n=this.modelValue.filter(function(a){return!x.equals(a,t,r.equalityKey)});this.updateModel(e,n)},clearFilter:function(){this.filterValue=null},hasFocusableElements:function(){return B.getFocusableElements(this.overlay,':not([data-p-hidden-focusable="true"])').length>0},isOptionMatched:function(e){var t;return this.isValidOption(e)&&typeof this.getOptionLabel(e)=="string"&&((t=this.getOptionLabel(e))===null||t===void 0?void 0:t.toLocaleLowerCase(this.filterLocale).startsWith(this.searchValue.toLocaleLowerCase(this.filterLocale)))},isValidOption:function(e){return 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this.hasSelectedOption&&(t?(r=this.findPrevSelectedOptionIndex(e),r=r===-1?this.findNextSelectedOptionIndex(e):r):(r=this.findNextSelectedOptionIndex(e),r=r===-1?this.findPrevSelectedOptionIndex(e):r)),r>-1?r:e},findFirstFocusedOptionIndex:function(){var e=this.findSelectedOptionIndex();return e<0?this.findFirstOptionIndex():e},findLastFocusedOptionIndex:function(){var e=this.findSelectedOptionIndex();return e<0?this.findLastOptionIndex():e},searchOptions:function(e){var t=this;this.searchValue=(this.searchValue||"")+e.key;var r=-1;x.isNotEmpty(this.searchValue)&&(this.focusedOptionIndex!==-1?(r=this.visibleOptions.slice(this.focusedOptionIndex).findIndex(function(n){return t.isOptionMatched(n)}),r=r===-1?this.visibleOptions.slice(0,this.focusedOptionIndex).findIndex(function(n){return t.isOptionMatched(n)}):r+this.focusedOptionIndex):r=this.visibleOptions.findIndex(function(n){return t.isOptionMatched(n)}),r===-1&&this.focusedOptionIndex===-1&&(r=this.findFirstFocusedOptionIndex()),r!==-1&&this.changeFocusedOptionIndex(e,r)),this.searchTimeout&&clearTimeout(this.searchTimeout),this.searchTimeout=setTimeout(function(){t.searchValue="",t.searchTimeout=null},500)},changeFocusedOptionIndex:function(e,t){this.focusedOptionIndex!==t&&(this.focusedOptionIndex=t,this.scrollInView(),this.selectOnFocus&&this.onOptionSelect(e,this.visibleOptions[t]))},scrollInView:function(){var e=this,t=arguments.length>0&&arguments[0]!==void 0?arguments[0]:-1;this.$nextTick(function(){var r=t!==-1?"".concat(e.id,"_").concat(t):e.focusedOptionId,n=B.findSingle(e.list,'li[id="'.concat(r,'"]'));n?n.scrollIntoView&&n.scrollIntoView({block:"nearest",inline:"nearest"}):e.virtualScrollerDisabled||e.virtualScroller&&e.virtualScroller.scrollToIndex(t!==-1?t:e.focusedOptionIndex)})},autoUpdateModel:function(){if(this.selectOnFocus&&this.autoOptionFocus&&!this.hasSelectedOption){this.focusedOptionIndex=this.findFirstFocusedOptionIndex();var e=this.getOptionValue(this.visibleOptions[this.focusedOptionIndex]);this.updateModel(null,[e])}},updateModel:function(e,t){this.$emit("update:modelValue",t),this.$emit("change",{originalEvent:e,value:t})},flatOptions:function(e){var t=this;return(e||[]).reduce(function(r,n,a){r.push({optionGroup:n,group:!0,index:a});var s=t.getOptionGroupChildren(n);return s&&s.forEach(function(i){return 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ef={Layout:Ri,enhanceApp({app:o,router:e,siteData:t}){o.use(hl,{theme:{preset:Xu}}),o.component("MultiSelect",wo),o.directive("FloatLabel",So)}};export{ef as R}; +`)},Uc={root:"p-floatlabel"},qc=z.extend({name:"floatlabel",theme:Gc,classes:Uc}),Yc={name:"BaseFloatLabel",extends:se,props:{},style:qc,provide:function(){return{$pcFloatLabel:this,$parentInstance:this}}},ko={name:"FloatLabel",extends:Yc,inheritAttrs:!1};function Zc(o,e,t,r,n,i){return h(),y("span",S({class:o.cx("root")},o.ptmi("root")),[L(o.$slots,"default")],16)}ko.render=Zc;var Xc={root:{transitionDuration:"{transition.duration}"},panel:{borderWidth:"0 0 1px 0",borderColor:"{content.border.color}"},header:{color:"{text.muted.color}",hoverColor:"{text.color}",activeColor:"{text.color}",padding:"1.125rem",fontWeight:"600",borderRadius:"0",borderWidth:"0",borderColor:"{content.border.color}",background:"{content.background}",hoverBackground:"{content.background}",activeBackground:"{content.background}",activeHoverBackground:"{content.background}",focusRing:{width:"{focus.ring.width}",style:"{focus.ring.style}",color:"{focus.ring.color}",offset:"{focus.ring.offset}",shadow:"{focus.ring.shadow}"},toggleIcon:{color:"{text.muted.color}",hoverColor:"{text.color}",activeColor:"{text.color}",activeHoverColor:"{text.color}"},first:{topBorderRadius:"{content.border.radius}",borderWidth:"0"},last:{bottomBorderRadius:"{content.border.radius}",activeBottomBorderRadius:"0"}},content:{borderWidth:"0",borderColor:"{content.border.color}",background:"{content.background}",color:"{text.color}",padding:"0 1.125rem 1.125rem 1.125rem"}},Qc={root:{background:"{form.field.background}",disabledBackground:"{form.field.disabled.background}",filledBackground:"{form.field.filled.background}",filledFocusBackground:"{form.field.filled.focus.background}",borderColor:"{form.field.border.color}",hoverBorderColor:"{form.field.hover.border.color}",focusBorderColor:"{form.field.focus.border.color}",invalidBorderColor:"{form.field.invalid.border.color}",color:"{form.field.color}",disabledColor:"{form.field.disabled.color}",placeholderColor:"{form.field.placeholder.color}",shadow:"{form.field.shadow}",paddingX:"{form.field.padding.x}",paddingY:"{form.field.padding.y}",borderRadius:"{form.field.border.radius}",focusRing:{width:"{form.field.focus.ring.width}",style:"{form.field.focus.ring.style}",color:"{form.field.focus.ring.color}",offset:"{form.field.focus.ring.offset}",shadow:"{form.field.focus.ring.shadow}"},transitionDuration:"{form.field.transition.duration}"},overlay:{background:"{overlay.select.background}",borderColor:"{overlay.select.border.color}",borderRadius:"{overlay.select.border.radius}",color:"{overlay.select.color}",shadow:"{overlay.select.shadow}"},list:{padding:"{list.padding}",gap:"{list.gap}"},option:{focusBackground:"{list.option.focus.background}",selectedBackground:"{list.option.selected.background}",selectedFocusBackground:"{list.option.selected.focus.background}",color:"{list.option.color}",focusColor:"{list.option.focus.color}",selectedColor:"{list.option.selected.color}",selectedFocusColor:"{list.option.selected.focus.color}",padding:"{list.option.padding}",borderRadius:"{list.option.border.radius}"},optionGroup:{background:"{list.option.group.background}",color:"{list.option.group.color}",fontWeight:"{list.option.group.font.weight}",padding:"{list.option.group.padding}"},dropdown:{width:"2.5rem",borderColor:"{form.field.border.color}",hoverBorderColor:"{form.field.border.color}",activeBorderColor:"{form.field.border.color}",borderRadius:"{form.field.border.radius}",focusRing:{width:"{focus.ring.width}",style:"{focus.ring.style}",color:"{focus.ring.color}",offset:"{focus.ring.offset}",shadow:"{focus.ring.shadow}"}},chip:{borderRadius:"{border.radius.sm}"},emptyMessage:{padding:"{list.option.padding}"},colorScheme:{light:{dropdown:{background:"{surface.100}",hoverBackground:"{surface.200}",activeBackground:"{surface.300}",color:"{surface.600}",hoverColor:"{surface.700}",activeColor:"{surface.800}"}},dark:{dropdown:{background:"{surface.800}",hoverBackground:"{surface.700}",activeBackground:"{surface.600}",color:"{surface.300}",hoverColor:"{surface.200}",activeColor:"{surface.100}"}}}},ed={root:{width:"2rem",height:"2rem",fontSize:"1rem",background:"{content.border.color}",borderRadius:"{content.border.radius}"},group:{borderColor:"{content.background}",offset:"-1rem"},lg:{width:"3rem",height:"3rem",fontSize:"1.5rem"},xl:{width:"4rem",height:"4rem",fontSize:"2rem"}},td={root:{borderRadius:"{border.radius.md}",padding:"0 0.5rem",fontSize:"0.75rem",fontWeight:"700",minWidth:"1.5rem",height:"1.5rem"},dot:{size:"0.5rem"},sm:{fontSize:"0.625rem",minWidth:"1.25rem",height:"1.25rem"},lg:{fontSize:"0.875rem",minWidth:"1.75rem",height:"1.75rem"},xl:{fontSize:"1rem",minWidth:"2rem",height:"2rem"},colorScheme:{light:{primary:{background:"{primary.color}",color:"{primary.contrast.color}"},secondary:{background:"{surface.100}",color:"{surface.600}"},success:{background:"{green.500}",color:"{surface.0}"},info:{background:"{sky.500}",color:"{surface.0}"},warn:{background:"{orange.500}",color:"{surface.0}"},danger:{background:"{red.500}",color:"{surface.0}"},contrast:{background:"{surface.950}",color:"{surface.0}"}},dark:{primary:{background:"{primary.color}",color:"{primary.contrast.color}"},secondary:{background:"{surface.800}",color:"{surface.300}"},success:{background:"{green.400}",color:"{green.950}"},info:{background:"{sky.400}",color:"{sky.950}"},warn:{background:"{orange.400}",color:"{orange.950}"},danger:{background:"{red.400}",color:"{red.950}"},contrast:{background:"{surface.0}",color:"{surface.950}"}}}},od={root:{borderRadius:"{content.border.radius}"}},rd={root:{padding:"1rem",background:"{content.background}",gap:"0.5rem",transitionDuration:"{transition.duration}"},item:{color:"{text.muted.color}",hoverColor:"{text.color}",iconColor:"{navigation.item.icon.color}",borderRadius:"{content.border.radius}",focusRing:{width:"{focus.ring.width}",style:"{focus.ring.style}",color:"{focus.ring.color}",offset:"{focus.ring.offset}",shadow:"{focus.ring.shadow}"}},separator:{color:"{navigation.item.icon.color}"}},nd={root:{borderRadius:"{form.field.border.radius}",roundedBorderRadius:"2rem",gap:"0.5rem",paddingX:"{form.field.padding.x}",paddingY:"{form.field.padding.y}",iconOnlyWidth:"2.5rem",sm:{fontSize:"0.875rem",paddingX:"0.625rem",paddingY:"0.375rem"},lg:{fontSize:"1.125rem",paddingX:"0.875rem",paddingY:"0.625rem"},label:{fontWeight:"500"},raisedShadow:"0 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",hoverBackground:"{surface.700}",activeBackground:"{surface.600}",borderColor:"{surface.800}",hoverBorderColor:"{surface.700}",activeBorderColor:"{surface.600}",color:"{surface.300}",hoverColor:"{surface.200}",activeColor:"{surface.100}",focusRing:{color:"{surface.300}",shadow:"none"}},info:{background:"{sky.400}",hoverBackground:"{sky.300}",activeBackground:"{sky.200}",borderColor:"{sky.400}",hoverBorderColor:"{sky.300}",activeBorderColor:"{sky.200}",color:"{sky.950}",hoverColor:"{sky.950}",activeColor:"{sky.950}",focusRing:{color:"{sky.400}",shadow:"none"}},success:{background:"{green.400}",hoverBackground:"{green.300}",activeBackground:"{green.200}",borderColor:"{green.400}",hoverBorderColor:"{green.300}",activeBorderColor:"{green.200}",color:"{green.950}",hoverColor:"{green.950}",activeColor:"{green.950}",focusRing:{color:"{green.400}",shadow:"none"}},warn:{background:"{orange.400}",hoverBackground:"{orange.300}",activeBackground:"{orange.200}",borderColor:"{orange.400}",hoverBorderColor:"{orange.300}",activeBorderColor:"{orange.200}",color:"{orange.950}",hoverColor:"{orange.950}",activeColor:"{orange.950}",focusRing:{color:"{orange.400}",shadow:"none"}},help:{background:"{purple.400}",hoverBackground:"{purple.300}",activeBackground:"{purple.200}",borderColor:"{purple.400}",hoverBorderColor:"{purple.300}",activeBorderColor:"{purple.200}",color:"{purple.950}",hoverColor:"{purple.950}",activeColor:"{purple.950}",focusRing:{color:"{purple.400}",shadow:"none"}},danger:{background:"{red.400}",hoverBackground:"{red.300}",activeBackground:"{red.200}",borderColor:"{red.400}",hoverBorderColor:"{red.300}",activeBorderColor:"{red.200}",color:"{red.950}",hoverColor:"{red.950}",activeColor:"{red.950}",focusRing:{color:"{red.400}",shadow:"none"}},contrast:{background:"{surface.0}",hoverBackground:"{surface.100}",activeBackground:"{surface.200}",borderColor:"{surface.0}",hoverBorderColor:"{surface.100}",activeBorderColor:"{surface.200}",color:"{surface.950}",hoverColor:"{surface.950}",activeColor:"{surface.950}",focusRing:{color:"{surface.0}",shadow:"none"}}},outlined:{primary:{hoverBackground:"color-mix(in 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m=JSON.parse('{"title":"","description":"","frontmatter":{"home":true},"headers":[],"relativePath":"index.md","filePath":"index.md"}'),n={name:"index.md"};function r(o,s,c,d,i,p){return a(),t("div")}const f=e(n,[["render",r]]);export{m as __pageData,f as default}; diff --git a/assets/papers_2013_ashenberg.md.C9dItqcV.js b/assets/papers_2013_ashenberg.md.DQMwPcgT.js similarity index 97% rename from assets/papers_2013_ashenberg.md.C9dItqcV.js rename to assets/papers_2013_ashenberg.md.DQMwPcgT.js index b60935e..b5db836 100644 --- a/assets/papers_2013_ashenberg.md.C9dItqcV.js +++ b/assets/papers_2013_ashenberg.md.DQMwPcgT.js @@ -1 +1 @@ -import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const y=JSON.parse('{"title":"Mutational effects on stability are largely conserved during protein evolution","description":"","frontmatter":{"layout":"paper","title":"Mutational effects on stability are largely conserved during protein evolution","date":"2013-12-24","authors":["Orr Ashenberg","Lizhi Ian Gong","Jesse D Bloom"],"journal":"PNAS","doi":"10.1073/pnas.1314781111","link":"https://www.pnas.org/doi/abs/10.1073/pnas.1314781111","image":"/assets/papers/2013_ashenberg.jpg","keywords":["Epistasis","Influenza"]},"headers":[],"relativePath":"papers/2013_ashenberg.md","filePath":"papers/2013_ashenberg.md"}'),n={name:"papers/2013_ashenberg.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Protein stability and folding are the result of cooperative interactions among many residues, yet phylogenetic approaches assume that sites are independent. This discrepancy has engendered concerns about large evolutionary shifts in mutational effects that might confound phylogenetic approaches. Here we experimentally investigate this issue by introducing the same mutations into a set of diverged homologs of the influenza nucleoprotein and measuring the effects on stability. We find that mutational effects on stability are largely conserved across the homologs. We reach qualitatively similar conclusions when we simulate protein evolution with molecular-mechanics force fields. Our results do not mean that proteins evolve without epistasis, which can still arise even when mutational stability effects are conserved. However, our findings indicate that large evolutionary shifts in mutational effects on stability are rare, at least among homologs with similar structures and functions. We suggest that properly describing the clearly observable and highly conserved amino acid preferences at individual sites is likely to be far more important for phylogenetic analyses than accounting for rare shifts in amino acid propensities due to site covariation.",-1),l=[o,r];function c(h,d,p,u,f,g){return s(),a("div",null,l)}const b=t(n,[["render",c]]);export{y as __pageData,b as default}; +import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const y=JSON.parse('{"title":"Mutational effects on stability are largely conserved during protein evolution","description":"","frontmatter":{"layout":"paper","title":"Mutational effects on stability are largely conserved during protein evolution","date":"2013-12-24","authors":["Orr Ashenberg","Lizhi Ian Gong","Jesse D Bloom"],"journal":"PNAS","doi":"10.1073/pnas.1314781111","link":"https://www.pnas.org/doi/abs/10.1073/pnas.1314781111","image":"/assets/papers/2013_ashenberg.jpg","keywords":["Epistasis","Influenza"]},"headers":[],"relativePath":"papers/2013_ashenberg.md","filePath":"papers/2013_ashenberg.md"}'),n={name:"papers/2013_ashenberg.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Protein stability and folding are the result of cooperative interactions among many residues, yet phylogenetic approaches assume that sites are independent. This discrepancy has engendered concerns about large evolutionary shifts in mutational effects that might confound phylogenetic approaches. Here we experimentally investigate this issue by introducing the same mutations into a set of diverged homologs of the influenza nucleoprotein and measuring the effects on stability. We find that mutational effects on stability are largely conserved across the homologs. We reach qualitatively similar conclusions when we simulate protein evolution with molecular-mechanics force fields. Our results do not mean that proteins evolve without epistasis, which can still arise even when mutational stability effects are conserved. However, our findings indicate that large evolutionary shifts in mutational effects on stability are rare, at least among homologs with similar structures and functions. We suggest that properly describing the clearly observable and highly conserved amino acid preferences at individual sites is likely to be far more important for phylogenetic analyses than accounting for rare shifts in amino acid propensities due to site covariation.",-1),l=[o,r];function c(h,d,p,u,f,g){return s(),a("div",null,l)}const b=t(n,[["render",c]]);export{y as __pageData,b as default}; diff --git a/assets/papers_2013_ashenberg.md.C9dItqcV.lean.js b/assets/papers_2013_ashenberg.md.DQMwPcgT.lean.js similarity index 97% rename from assets/papers_2013_ashenberg.md.C9dItqcV.lean.js rename to assets/papers_2013_ashenberg.md.DQMwPcgT.lean.js index b60935e..b5db836 100644 --- a/assets/papers_2013_ashenberg.md.C9dItqcV.lean.js +++ b/assets/papers_2013_ashenberg.md.DQMwPcgT.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const y=JSON.parse('{"title":"Mutational effects on stability are largely conserved during protein evolution","description":"","frontmatter":{"layout":"paper","title":"Mutational effects on stability are largely conserved during protein evolution","date":"2013-12-24","authors":["Orr Ashenberg","Lizhi Ian Gong","Jesse D Bloom"],"journal":"PNAS","doi":"10.1073/pnas.1314781111","link":"https://www.pnas.org/doi/abs/10.1073/pnas.1314781111","image":"/assets/papers/2013_ashenberg.jpg","keywords":["Epistasis","Influenza"]},"headers":[],"relativePath":"papers/2013_ashenberg.md","filePath":"papers/2013_ashenberg.md"}'),n={name:"papers/2013_ashenberg.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Protein stability and folding are the result of cooperative interactions among many residues, yet phylogenetic approaches assume that sites are independent. This discrepancy has engendered concerns about large evolutionary shifts in mutational effects that might confound phylogenetic approaches. Here we experimentally investigate this issue by introducing the same mutations into a set of diverged homologs of the influenza nucleoprotein and measuring the effects on stability. We find that mutational effects on stability are largely conserved across the homologs. We reach qualitatively similar conclusions when we simulate protein evolution with molecular-mechanics force fields. Our results do not mean that proteins evolve without epistasis, which can still arise even when mutational stability effects are conserved. However, our findings indicate that large evolutionary shifts in mutational effects on stability are rare, at least among homologs with similar structures and functions. We suggest that properly describing the clearly observable and highly conserved amino acid preferences at individual sites is likely to be far more important for phylogenetic analyses than accounting for rare shifts in amino acid propensities due to site covariation.",-1),l=[o,r];function c(h,d,p,u,f,g){return s(),a("div",null,l)}const b=t(n,[["render",c]]);export{y as __pageData,b as default}; +import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const y=JSON.parse('{"title":"Mutational effects on stability are largely conserved during protein evolution","description":"","frontmatter":{"layout":"paper","title":"Mutational effects on stability are largely conserved during protein evolution","date":"2013-12-24","authors":["Orr Ashenberg","Lizhi Ian Gong","Jesse D Bloom"],"journal":"PNAS","doi":"10.1073/pnas.1314781111","link":"https://www.pnas.org/doi/abs/10.1073/pnas.1314781111","image":"/assets/papers/2013_ashenberg.jpg","keywords":["Epistasis","Influenza"]},"headers":[],"relativePath":"papers/2013_ashenberg.md","filePath":"papers/2013_ashenberg.md"}'),n={name:"papers/2013_ashenberg.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Protein stability and folding are the result of cooperative interactions among many residues, yet phylogenetic approaches assume that sites are independent. This discrepancy has engendered concerns about large evolutionary shifts in mutational effects that might confound phylogenetic approaches. Here we experimentally investigate this issue by introducing the same mutations into a set of diverged homologs of the influenza nucleoprotein and measuring the effects on stability. We find that mutational effects on stability are largely conserved across the homologs. We reach qualitatively similar conclusions when we simulate protein evolution with molecular-mechanics force fields. Our results do not mean that proteins evolve without epistasis, which can still arise even when mutational stability effects are conserved. However, our findings indicate that large evolutionary shifts in mutational effects on stability are rare, at least among homologs with similar structures and functions. We suggest that properly describing the clearly observable and highly conserved amino acid preferences at individual sites is likely to be far more important for phylogenetic analyses than accounting for rare shifts in amino acid propensities due to site covariation.",-1),l=[o,r];function c(h,d,p,u,f,g){return s(),a("div",null,l)}const b=t(n,[["render",c]]);export{y as __pageData,b as default}; diff --git a/assets/papers_2013_gong.md.KjIciAby.js b/assets/papers_2013_gong.md.PyD3I5qV.js similarity index 97% rename from assets/papers_2013_gong.md.KjIciAby.js rename to assets/papers_2013_gong.md.PyD3I5qV.js index 92d40d3..6f7ab9a 100644 --- a/assets/papers_2013_gong.md.KjIciAby.js +++ b/assets/papers_2013_gong.md.PyD3I5qV.js @@ -1 +1 @@ -import{_ as t,c as a,o as i,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Stability-mediated epistasis constrains the evolution of an influenza protein","description":"","frontmatter":{"layout":"paper","title":"Stability-mediated epistasis constrains the evolution of an influenza protein","date":"2013-05-14","authors":["Lizhi Ian Gong","Marc A Suchard","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.7554/eLife.00631.001","link":"https://elifesciences.org/articles/631","image":"/assets/papers/2013_gong.jpg","keywords":["Influenza","Epistasis"]},"headers":[],"relativePath":"papers/2013_gong.md","filePath":"papers/2013_gong.md"}'),n={name:"papers/2013_gong.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"John Maynard Smith compared protein evolution to the game where one word is converted into another a single letter at a time, with the constraint that all intermediates are words: WORD→WORE→GORE→GONE→GENE. In this analogy, epistasis constrains evolution, with some mutations tolerated only after the occurrence of others. To test whether epistasis similarly constrains actual protein evolution, we created all intermediates along a 39-mutation evolutionary trajectory of influenza nucleoprotein, and also introduced each mutation individually into the parent. Several mutations were deleterious to the parent despite becoming fixed during evolution without negative impact. These mutations were destabilizing, and were preceded or accompanied by stabilizing mutations that alleviated their adverse effects. The constrained mutations occurred at sites enriched in T-cell epitopes, suggesting they promote viral immune escape. Our results paint a coherent portrait of epistasis during nucleoprotein evolution, with stabilizing mutations permitting otherwise inaccessible destabilizing mutations which are sometimes of adaptive value.",-1),l=[s,r];function c(d,p,u,h,m,g){return i(),a("div",null,l)}const v=t(n,[["render",c]]);export{_ as __pageData,v as default}; +import{_ as t,c as a,o as i,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Stability-mediated epistasis constrains the evolution of an influenza protein","description":"","frontmatter":{"layout":"paper","title":"Stability-mediated epistasis constrains the evolution of an influenza protein","date":"2013-05-14","authors":["Lizhi Ian Gong","Marc A Suchard","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.7554/eLife.00631.001","link":"https://elifesciences.org/articles/631","image":"/assets/papers/2013_gong.jpg","keywords":["Influenza","Epistasis"]},"headers":[],"relativePath":"papers/2013_gong.md","filePath":"papers/2013_gong.md"}'),n={name:"papers/2013_gong.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"John Maynard Smith compared protein evolution to the game where one word is converted into another a single letter at a time, with the constraint that all intermediates are words: WORD→WORE→GORE→GONE→GENE. In this analogy, epistasis constrains evolution, with some mutations tolerated only after the occurrence of others. To test whether epistasis similarly constrains actual protein evolution, we created all intermediates along a 39-mutation evolutionary trajectory of influenza nucleoprotein, and also introduced each mutation individually into the parent. Several mutations were deleterious to the parent despite becoming fixed during evolution without negative impact. These mutations were destabilizing, and were preceded or accompanied by stabilizing mutations that alleviated their adverse effects. The constrained mutations occurred at sites enriched in T-cell epitopes, suggesting they promote viral immune escape. Our results paint a coherent portrait of epistasis during nucleoprotein evolution, with stabilizing mutations permitting otherwise inaccessible destabilizing mutations which are sometimes of adaptive value.",-1),l=[s,r];function c(d,p,u,h,m,g){return i(),a("div",null,l)}const v=t(n,[["render",c]]);export{_ as __pageData,v as default}; diff --git a/assets/papers_2013_gong.md.KjIciAby.lean.js b/assets/papers_2013_gong.md.PyD3I5qV.lean.js similarity index 97% rename from assets/papers_2013_gong.md.KjIciAby.lean.js rename to assets/papers_2013_gong.md.PyD3I5qV.lean.js index 92d40d3..6f7ab9a 100644 --- a/assets/papers_2013_gong.md.KjIciAby.lean.js +++ b/assets/papers_2013_gong.md.PyD3I5qV.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as i,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Stability-mediated epistasis constrains the evolution of an influenza protein","description":"","frontmatter":{"layout":"paper","title":"Stability-mediated epistasis constrains the evolution of an influenza protein","date":"2013-05-14","authors":["Lizhi Ian Gong","Marc A Suchard","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.7554/eLife.00631.001","link":"https://elifesciences.org/articles/631","image":"/assets/papers/2013_gong.jpg","keywords":["Influenza","Epistasis"]},"headers":[],"relativePath":"papers/2013_gong.md","filePath":"papers/2013_gong.md"}'),n={name:"papers/2013_gong.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"John Maynard Smith compared protein evolution to the game where one word is converted into another a single letter at a time, with the constraint that all intermediates are words: WORD→WORE→GORE→GONE→GENE. In this analogy, epistasis constrains evolution, with some mutations tolerated only after the occurrence of others. To test whether epistasis similarly constrains actual protein evolution, we created all intermediates along a 39-mutation evolutionary trajectory of influenza nucleoprotein, and also introduced each mutation individually into the parent. Several mutations were deleterious to the parent despite becoming fixed during evolution without negative impact. These mutations were destabilizing, and were preceded or accompanied by stabilizing mutations that alleviated their adverse effects. The constrained mutations occurred at sites enriched in T-cell epitopes, suggesting they promote viral immune escape. Our results paint a coherent portrait of epistasis during nucleoprotein evolution, with stabilizing mutations permitting otherwise inaccessible destabilizing mutations which are sometimes of adaptive value.",-1),l=[s,r];function c(d,p,u,h,m,g){return i(),a("div",null,l)}const v=t(n,[["render",c]]);export{_ as __pageData,v as default}; +import{_ as t,c as a,o as i,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Stability-mediated epistasis constrains the evolution of an influenza protein","description":"","frontmatter":{"layout":"paper","title":"Stability-mediated epistasis constrains the evolution of an influenza protein","date":"2013-05-14","authors":["Lizhi Ian Gong","Marc A Suchard","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.7554/eLife.00631.001","link":"https://elifesciences.org/articles/631","image":"/assets/papers/2013_gong.jpg","keywords":["Influenza","Epistasis"]},"headers":[],"relativePath":"papers/2013_gong.md","filePath":"papers/2013_gong.md"}'),n={name:"papers/2013_gong.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"John Maynard Smith compared protein evolution to the game where one word is converted into another a single letter at a time, with the constraint that all intermediates are words: WORD→WORE→GORE→GONE→GENE. In this analogy, epistasis constrains evolution, with some mutations tolerated only after the occurrence of others. To test whether epistasis similarly constrains actual protein evolution, we created all intermediates along a 39-mutation evolutionary trajectory of influenza nucleoprotein, and also introduced each mutation individually into the parent. Several mutations were deleterious to the parent despite becoming fixed during evolution without negative impact. These mutations were destabilizing, and were preceded or accompanied by stabilizing mutations that alleviated their adverse effects. The constrained mutations occurred at sites enriched in T-cell epitopes, suggesting they promote viral immune escape. Our results paint a coherent portrait of epistasis during nucleoprotein evolution, with stabilizing mutations permitting otherwise inaccessible destabilizing mutations which are sometimes of adaptive value.",-1),l=[s,r];function c(d,p,u,h,m,g){return i(),a("div",null,l)}const v=t(n,[["render",c]]);export{_ as __pageData,v as default}; diff --git a/assets/papers_2013_hooper.md.ChN7rCDv.js b/assets/papers_2013_hooper.md.Cd1R1SDU.js similarity index 97% rename from assets/papers_2013_hooper.md.ChN7rCDv.js rename to assets/papers_2013_hooper.md.Cd1R1SDU.js index c1750fe..1d3dd9e 100644 --- a/assets/papers_2013_hooper.md.ChN7rCDv.js +++ b/assets/papers_2013_hooper.md.Cd1R1SDU.js @@ -1 +1 @@ -import{_ as t,c as a,o as r,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein","description":"","frontmatter":{"layout":"paper","title":"A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein","date":"2013-12-01","authors":["Kathryn A Hooper","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.01889-13","link":"https://journals.asm.org/doi/full/10.1128/jvi.01889-13","image":"/assets/papers/2013_hooper.jpg","keywords":["Influenza"]},"headers":[],"relativePath":"papers/2013_hooper.md","filePath":"papers/2013_hooper.md"}'),n={name:"papers/2013_hooper.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"In the vast majority of influenza A viruses characterized to date, hemagglutinin (HA) is the receptor-binding and fusion protein, whereas neuraminidase (NA) is a receptor-cleaving protein that facilitates viral release but is expendable for entry. However, the NAs of some recent human H3N2 isolates have acquired receptor-binding activity via the mutation D151G, although these isolates also appear to retain the ability to bind receptors via HA. We report here the laboratory generation of a mutation (G147R) that enables an N1 NA to completely co-opt the receptor-binding function normally performed by HA. Viruses with this mutant NA grow to high titers even in the presence of extensive mutations to conserved residues in HA's receptor-binding pocket. When the receptor-binding NA is paired with this binding-deficient HA, viral infectivity and red blood cell agglutination are blocked by NA inhibitors. Furthermore, virus-like particles expressing only the receptor-binding NA agglutinate red blood cells in an NA-dependent manner. Although the G147R NA receptor-binding mutant virus that we characterize is a laboratory creation, this same mutation is found in several natural clusters of H1N1 and H5N1 viruses. Our results demonstrate that, at least in tissue culture, influenza virus receptor-binding activity can be entirely shifted from HA to NA.",-1),l=[o,s];function c(h,d,p,u,m,b){return r(),a("div",null,l)}const v=t(n,[["render",c]]);export{g as __pageData,v as default}; +import{_ as t,c as a,o as r,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein","description":"","frontmatter":{"layout":"paper","title":"A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein","date":"2013-12-01","authors":["Kathryn A Hooper","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.01889-13","link":"https://journals.asm.org/doi/full/10.1128/jvi.01889-13","image":"/assets/papers/2013_hooper.jpg","keywords":["Influenza"]},"headers":[],"relativePath":"papers/2013_hooper.md","filePath":"papers/2013_hooper.md"}'),n={name:"papers/2013_hooper.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"In the vast majority of influenza A viruses characterized to date, hemagglutinin (HA) is the receptor-binding and fusion protein, whereas neuraminidase (NA) is a receptor-cleaving protein that facilitates viral release but is expendable for entry. However, the NAs of some recent human H3N2 isolates have acquired receptor-binding activity via the mutation D151G, although these isolates also appear to retain the ability to bind receptors via HA. We report here the laboratory generation of a mutation (G147R) that enables an N1 NA to completely co-opt the receptor-binding function normally performed by HA. Viruses with this mutant NA grow to high titers even in the presence of extensive mutations to conserved residues in HA's receptor-binding pocket. When the receptor-binding NA is paired with this binding-deficient HA, viral infectivity and red blood cell agglutination are blocked by NA inhibitors. Furthermore, virus-like particles expressing only the receptor-binding NA agglutinate red blood cells in an NA-dependent manner. Although the G147R NA receptor-binding mutant virus that we characterize is a laboratory creation, this same mutation is found in several natural clusters of H1N1 and H5N1 viruses. Our results demonstrate that, at least in tissue culture, influenza virus receptor-binding activity can be entirely shifted from HA to NA.",-1),l=[o,s];function c(h,d,p,u,m,b){return r(),a("div",null,l)}const v=t(n,[["render",c]]);export{g as __pageData,v as default}; diff --git a/assets/papers_2013_hooper.md.ChN7rCDv.lean.js b/assets/papers_2013_hooper.md.Cd1R1SDU.lean.js similarity index 97% rename from assets/papers_2013_hooper.md.ChN7rCDv.lean.js rename to assets/papers_2013_hooper.md.Cd1R1SDU.lean.js index c1750fe..1d3dd9e 100644 --- a/assets/papers_2013_hooper.md.ChN7rCDv.lean.js +++ b/assets/papers_2013_hooper.md.Cd1R1SDU.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as r,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein","description":"","frontmatter":{"layout":"paper","title":"A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein","date":"2013-12-01","authors":["Kathryn A Hooper","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.01889-13","link":"https://journals.asm.org/doi/full/10.1128/jvi.01889-13","image":"/assets/papers/2013_hooper.jpg","keywords":["Influenza"]},"headers":[],"relativePath":"papers/2013_hooper.md","filePath":"papers/2013_hooper.md"}'),n={name:"papers/2013_hooper.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"In the vast majority of influenza A viruses characterized to date, hemagglutinin (HA) is the receptor-binding and fusion protein, whereas neuraminidase (NA) is a receptor-cleaving protein that facilitates viral release but is expendable for entry. However, the NAs of some recent human H3N2 isolates have acquired receptor-binding activity via the mutation D151G, although these isolates also appear to retain the ability to bind receptors via HA. We report here the laboratory generation of a mutation (G147R) that enables an N1 NA to completely co-opt the receptor-binding function normally performed by HA. Viruses with this mutant NA grow to high titers even in the presence of extensive mutations to conserved residues in HA's receptor-binding pocket. When the receptor-binding NA is paired with this binding-deficient HA, viral infectivity and red blood cell agglutination are blocked by NA inhibitors. Furthermore, virus-like particles expressing only the receptor-binding NA agglutinate red blood cells in an NA-dependent manner. Although the G147R NA receptor-binding mutant virus that we characterize is a laboratory creation, this same mutation is found in several natural clusters of H1N1 and H5N1 viruses. Our results demonstrate that, at least in tissue culture, influenza virus receptor-binding activity can be entirely shifted from HA to NA.",-1),l=[o,s];function c(h,d,p,u,m,b){return r(),a("div",null,l)}const v=t(n,[["render",c]]);export{g as __pageData,v as default}; +import{_ as t,c as a,o as r,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein","description":"","frontmatter":{"layout":"paper","title":"A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein","date":"2013-12-01","authors":["Kathryn A Hooper","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.01889-13","link":"https://journals.asm.org/doi/full/10.1128/jvi.01889-13","image":"/assets/papers/2013_hooper.jpg","keywords":["Influenza"]},"headers":[],"relativePath":"papers/2013_hooper.md","filePath":"papers/2013_hooper.md"}'),n={name:"papers/2013_hooper.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"In the vast majority of influenza A viruses characterized to date, hemagglutinin (HA) is the receptor-binding and fusion protein, whereas neuraminidase (NA) is a receptor-cleaving protein that facilitates viral release but is expendable for entry. However, the NAs of some recent human H3N2 isolates have acquired receptor-binding activity via the mutation D151G, although these isolates also appear to retain the ability to bind receptors via HA. We report here the laboratory generation of a mutation (G147R) that enables an N1 NA to completely co-opt the receptor-binding function normally performed by HA. Viruses with this mutant NA grow to high titers even in the presence of extensive mutations to conserved residues in HA's receptor-binding pocket. When the receptor-binding NA is paired with this binding-deficient HA, viral infectivity and red blood cell agglutination are blocked by NA inhibitors. Furthermore, virus-like particles expressing only the receptor-binding NA agglutinate red blood cells in an NA-dependent manner. Although the G147R NA receptor-binding mutant virus that we characterize is a laboratory creation, this same mutation is found in several natural clusters of H1N1 and H5N1 viruses. Our results demonstrate that, at least in tissue culture, influenza virus receptor-binding activity can be entirely shifted from HA to NA.",-1),l=[o,s];function c(h,d,p,u,m,b){return r(),a("div",null,l)}const v=t(n,[["render",c]]);export{g as __pageData,v as default}; diff --git a/assets/papers_2014_bloom_a.md.BRnRJww4.js b/assets/papers_2014_bloom_a.md.TW6XA02c.js similarity index 95% rename from assets/papers_2014_bloom_a.md.BRnRJww4.js rename to assets/papers_2014_bloom_a.md.TW6XA02c.js index 96268fc..6fad5d1 100644 --- a/assets/papers_2014_bloom_a.md.BRnRJww4.js +++ b/assets/papers_2014_bloom_a.md.TW6XA02c.js @@ -1 +1 @@ -import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs","description":"","frontmatter":{"layout":"paper","title":"An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs","date":"2014-10-01","authors":["Jesse D Bloom"],"journal":"Molecular biology and evolution","doi":"10.1093/molbev/msu220","link":"https://academic.oup.com/mbe/article/31/10/2753/1015257","image":"/assets/papers/2014_bloom_a.jpg","keywords":["Phylogenetics"]},"headers":[],"relativePath":"papers/2014_bloom_a.md","filePath":"papers/2014_bloom_a.md"}'),s={name:"papers/2014_bloom_a.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Phylogenetic analyses of molecular data require a quantitative model for how sequences evolve. Traditionally, the details of the site-specific selection that governs sequence evolution are not known a priori, making it challenging to create evolutionary models that adequately capture the heterogeneity of selection at different sites. However, recent advances in high-throughput experiments have made it possible to quantify the effects of all single mutations on gene function. I have previously shown that such high-throughput experiments can be combined with knowledge of underlying mutation rates to create a parameter-free evolutionary model that describes the phylogeny of influenza nucleoprotein far better than commonly used existing models. Here, I extend this work by showing that published experimental data on TEM-1 beta-lactamase (Firnberg E, Labonte JW, Gray JJ, Ostermeier M. 2014. A comprehensive, high-resolution map of a gene’s fitness landscape. Mol Biol Evol. 31:1581–1592) can be combined with a few mutation rate parameters to create an evolutionary model that describes beta-lactamase phylogenies much better than most common existing models. This experimentally informed evolutionary model is superior even for homologs that are substantially diverged (about 35% divergence at the protein level) from the TEM-1 parent that was the subject of the experimental study. These results suggest that experimental measurements can inform phylogenetic evolutionary models that are applicable to homologs that span a substantial range of sequence divergence.",-1),l=[i,r];function m(c,h,d,p,u,g){return o(),a("div",null,l)}const y=t(s,[["render",m]]);export{b as __pageData,y as default}; +import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs","description":"","frontmatter":{"layout":"paper","title":"An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs","date":"2014-10-01","authors":["Jesse D Bloom"],"journal":"Molecular biology and evolution","doi":"10.1093/molbev/msu220","link":"https://academic.oup.com/mbe/article/31/10/2753/1015257","image":"/assets/papers/2014_bloom_a.jpg","keywords":["Phylogenetics"]},"headers":[],"relativePath":"papers/2014_bloom_a.md","filePath":"papers/2014_bloom_a.md"}'),s={name:"papers/2014_bloom_a.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Phylogenetic analyses of molecular data require a quantitative model for how sequences evolve. Traditionally, the details of the site-specific selection that governs sequence evolution are not known a priori, making it challenging to create evolutionary models that adequately capture the heterogeneity of selection at different sites. However, recent advances in high-throughput experiments have made it possible to quantify the effects of all single mutations on gene function. I have previously shown that such high-throughput experiments can be combined with knowledge of underlying mutation rates to create a parameter-free evolutionary model that describes the phylogeny of influenza nucleoprotein far better than commonly used existing models. Here, I extend this work by showing that published experimental data on TEM-1 beta-lactamase (Firnberg E, Labonte JW, Gray JJ, Ostermeier M. 2014. A comprehensive, high-resolution map of a gene’s fitness landscape. Mol Biol Evol. 31:1581–1592) can be combined with a few mutation rate parameters to create an evolutionary model that describes beta-lactamase phylogenies much better than most common existing models. This experimentally informed evolutionary model is superior even for homologs that are substantially diverged (about 35% divergence at the protein level) from the TEM-1 parent that was the subject of the experimental study. These results suggest that experimental measurements can inform phylogenetic evolutionary models that are applicable to homologs that span a substantial range of sequence divergence.",-1),l=[i,r];function m(c,h,d,p,u,g){return o(),a("div",null,l)}const y=t(s,[["render",m]]);export{b as __pageData,y as default}; diff --git a/assets/papers_2014_bloom_a.md.BRnRJww4.lean.js b/assets/papers_2014_bloom_a.md.TW6XA02c.lean.js similarity index 95% rename from assets/papers_2014_bloom_a.md.BRnRJww4.lean.js rename to assets/papers_2014_bloom_a.md.TW6XA02c.lean.js index 96268fc..6fad5d1 100644 --- a/assets/papers_2014_bloom_a.md.BRnRJww4.lean.js +++ b/assets/papers_2014_bloom_a.md.TW6XA02c.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs","description":"","frontmatter":{"layout":"paper","title":"An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs","date":"2014-10-01","authors":["Jesse D Bloom"],"journal":"Molecular biology and evolution","doi":"10.1093/molbev/msu220","link":"https://academic.oup.com/mbe/article/31/10/2753/1015257","image":"/assets/papers/2014_bloom_a.jpg","keywords":["Phylogenetics"]},"headers":[],"relativePath":"papers/2014_bloom_a.md","filePath":"papers/2014_bloom_a.md"}'),s={name:"papers/2014_bloom_a.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Phylogenetic analyses of molecular data require a quantitative model for how sequences evolve. Traditionally, the details of the site-specific selection that governs sequence evolution are not known a priori, making it challenging to create evolutionary models that adequately capture the heterogeneity of selection at different sites. However, recent advances in high-throughput experiments have made it possible to quantify the effects of all single mutations on gene function. I have previously shown that such high-throughput experiments can be combined with knowledge of underlying mutation rates to create a parameter-free evolutionary model that describes the phylogeny of influenza nucleoprotein far better than commonly used existing models. Here, I extend this work by showing that published experimental data on TEM-1 beta-lactamase (Firnberg E, Labonte JW, Gray JJ, Ostermeier M. 2014. A comprehensive, high-resolution map of a gene’s fitness landscape. Mol Biol Evol. 31:1581–1592) can be combined with a few mutation rate parameters to create an evolutionary model that describes beta-lactamase phylogenies much better than most common existing models. This experimentally informed evolutionary model is superior even for homologs that are substantially diverged (about 35% divergence at the protein level) from the TEM-1 parent that was the subject of the experimental study. These results suggest that experimental measurements can inform phylogenetic evolutionary models that are applicable to homologs that span a substantial range of sequence divergence.",-1),l=[i,r];function m(c,h,d,p,u,g){return o(),a("div",null,l)}const y=t(s,[["render",m]]);export{b as __pageData,y as default}; +import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs","description":"","frontmatter":{"layout":"paper","title":"An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs","date":"2014-10-01","authors":["Jesse D Bloom"],"journal":"Molecular biology and evolution","doi":"10.1093/molbev/msu220","link":"https://academic.oup.com/mbe/article/31/10/2753/1015257","image":"/assets/papers/2014_bloom_a.jpg","keywords":["Phylogenetics"]},"headers":[],"relativePath":"papers/2014_bloom_a.md","filePath":"papers/2014_bloom_a.md"}'),s={name:"papers/2014_bloom_a.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Phylogenetic analyses of molecular data require a quantitative model for how sequences evolve. Traditionally, the details of the site-specific selection that governs sequence evolution are not known a priori, making it challenging to create evolutionary models that adequately capture the heterogeneity of selection at different sites. However, recent advances in high-throughput experiments have made it possible to quantify the effects of all single mutations on gene function. I have previously shown that such high-throughput experiments can be combined with knowledge of underlying mutation rates to create a parameter-free evolutionary model that describes the phylogeny of influenza nucleoprotein far better than commonly used existing models. Here, I extend this work by showing that published experimental data on TEM-1 beta-lactamase (Firnberg E, Labonte JW, Gray JJ, Ostermeier M. 2014. A comprehensive, high-resolution map of a gene’s fitness landscape. Mol Biol Evol. 31:1581–1592) can be combined with a few mutation rate parameters to create an evolutionary model that describes beta-lactamase phylogenies much better than most common existing models. This experimentally informed evolutionary model is superior even for homologs that are substantially diverged (about 35% divergence at the protein level) from the TEM-1 parent that was the subject of the experimental study. These results suggest that experimental measurements can inform phylogenetic evolutionary models that are applicable to homologs that span a substantial range of sequence divergence.",-1),l=[i,r];function m(c,h,d,p,u,g){return o(),a("div",null,l)}const y=t(s,[["render",m]]);export{b as __pageData,y as default}; diff --git a/assets/papers_2014_bloom_b.md.D5Kmd9bp.js b/assets/papers_2014_bloom_b.md.Cm1oDw8Z.js similarity index 93% rename from assets/papers_2014_bloom_b.md.D5Kmd9bp.js rename to assets/papers_2014_bloom_b.md.Cm1oDw8Z.js index b43c5c1..8a1b956 100644 --- a/assets/papers_2014_bloom_b.md.D5Kmd9bp.js +++ b/assets/papers_2014_bloom_b.md.Cm1oDw8Z.js @@ -1 +1 @@ -import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const f=JSON.parse('{"title":"An experimentally determined evolutionary model dramatically improves phylogenetic fit","description":"","frontmatter":{"layout":"paper","title":"An experimentally determined evolutionary model dramatically improves phylogenetic fit","date":"2014-08-01","authors":["Jesse D Bloom"],"journal":"Molecular Biology and Evolution","doi":"10.1093/molbev/msu173","link":"https://academic.oup.com/mbe/article/31/8/1956/2925795","image":"/assets/papers/2014_bloom_b.jpg","keywords":["Phylogenetics"]},"headers":[],"relativePath":"papers/2014_bloom_b.md","filePath":"papers/2014_bloom_b.md"}'),r={name:"papers/2014_bloom_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"All modern approaches to molecular phylogenetics require a quantitative model for how genes evolve. Unfortunately, existing evolutionary models do not realistically represent the site-heterogeneous selection that governs actual sequence change. Attempts to remedy this problem have involved augmenting these models with a burgeoning number of free parameters. Here, I demonstrate an alternative: Experimental determination of a parameter-free evolutionary model via mutagenesis, functional selection, and deep sequencing. Using this strategy, I create an evolutionary model for influenza nucleoprotein that describes the gene phylogeny far better than existing models with dozens or even hundreds of free parameters. Emerging high-throughput experimental strategies such as the one employed here provide fundamentally new information that has the potential to transform the sensitivity of phylogenetic and genetic analyses.",-1),l=[s,i];function m(d,c,p,h,u,g){return o(),a("div",null,l)}const y=t(r,[["render",m]]);export{f as __pageData,y as default}; +import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const f=JSON.parse('{"title":"An experimentally determined evolutionary model dramatically improves phylogenetic fit","description":"","frontmatter":{"layout":"paper","title":"An experimentally determined evolutionary model dramatically improves phylogenetic fit","date":"2014-08-01","authors":["Jesse D Bloom"],"journal":"Molecular Biology and Evolution","doi":"10.1093/molbev/msu173","link":"https://academic.oup.com/mbe/article/31/8/1956/2925795","image":"/assets/papers/2014_bloom_b.jpg","keywords":["Phylogenetics"]},"headers":[],"relativePath":"papers/2014_bloom_b.md","filePath":"papers/2014_bloom_b.md"}'),r={name:"papers/2014_bloom_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"All modern approaches to molecular phylogenetics require a quantitative model for how genes evolve. Unfortunately, existing evolutionary models do not realistically represent the site-heterogeneous selection that governs actual sequence change. Attempts to remedy this problem have involved augmenting these models with a burgeoning number of free parameters. Here, I demonstrate an alternative: Experimental determination of a parameter-free evolutionary model via mutagenesis, functional selection, and deep sequencing. Using this strategy, I create an evolutionary model for influenza nucleoprotein that describes the gene phylogeny far better than existing models with dozens or even hundreds of free parameters. Emerging high-throughput experimental strategies such as the one employed here provide fundamentally new information that has the potential to transform the sensitivity of phylogenetic and genetic analyses.",-1),l=[s,i];function m(d,c,p,h,u,g){return o(),a("div",null,l)}const y=t(r,[["render",m]]);export{f as __pageData,y as default}; diff --git a/assets/papers_2014_bloom_b.md.D5Kmd9bp.lean.js b/assets/papers_2014_bloom_b.md.Cm1oDw8Z.lean.js similarity index 93% rename from assets/papers_2014_bloom_b.md.D5Kmd9bp.lean.js rename to assets/papers_2014_bloom_b.md.Cm1oDw8Z.lean.js index b43c5c1..8a1b956 100644 --- a/assets/papers_2014_bloom_b.md.D5Kmd9bp.lean.js +++ b/assets/papers_2014_bloom_b.md.Cm1oDw8Z.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const f=JSON.parse('{"title":"An experimentally determined evolutionary model dramatically improves phylogenetic fit","description":"","frontmatter":{"layout":"paper","title":"An experimentally determined evolutionary model dramatically improves phylogenetic fit","date":"2014-08-01","authors":["Jesse D Bloom"],"journal":"Molecular Biology and Evolution","doi":"10.1093/molbev/msu173","link":"https://academic.oup.com/mbe/article/31/8/1956/2925795","image":"/assets/papers/2014_bloom_b.jpg","keywords":["Phylogenetics"]},"headers":[],"relativePath":"papers/2014_bloom_b.md","filePath":"papers/2014_bloom_b.md"}'),r={name:"papers/2014_bloom_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"All modern approaches to molecular phylogenetics require a quantitative model for how genes evolve. Unfortunately, existing evolutionary models do not realistically represent the site-heterogeneous selection that governs actual sequence change. Attempts to remedy this problem have involved augmenting these models with a burgeoning number of free parameters. Here, I demonstrate an alternative: Experimental determination of a parameter-free evolutionary model via mutagenesis, functional selection, and deep sequencing. Using this strategy, I create an evolutionary model for influenza nucleoprotein that describes the gene phylogeny far better than existing models with dozens or even hundreds of free parameters. Emerging high-throughput experimental strategies such as the one employed here provide fundamentally new information that has the potential to transform the sensitivity of phylogenetic and genetic analyses.",-1),l=[s,i];function m(d,c,p,h,u,g){return o(),a("div",null,l)}const y=t(r,[["render",m]]);export{f as __pageData,y as default}; +import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const f=JSON.parse('{"title":"An experimentally determined evolutionary model dramatically improves phylogenetic fit","description":"","frontmatter":{"layout":"paper","title":"An experimentally determined evolutionary model dramatically improves phylogenetic fit","date":"2014-08-01","authors":["Jesse D Bloom"],"journal":"Molecular Biology and Evolution","doi":"10.1093/molbev/msu173","link":"https://academic.oup.com/mbe/article/31/8/1956/2925795","image":"/assets/papers/2014_bloom_b.jpg","keywords":["Phylogenetics"]},"headers":[],"relativePath":"papers/2014_bloom_b.md","filePath":"papers/2014_bloom_b.md"}'),r={name:"papers/2014_bloom_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"All modern approaches to molecular phylogenetics require a quantitative model for how genes evolve. Unfortunately, existing evolutionary models do not realistically represent the site-heterogeneous selection that governs actual sequence change. Attempts to remedy this problem have involved augmenting these models with a burgeoning number of free parameters. Here, I demonstrate an alternative: Experimental determination of a parameter-free evolutionary model via mutagenesis, functional selection, and deep sequencing. Using this strategy, I create an evolutionary model for influenza nucleoprotein that describes the gene phylogeny far better than existing models with dozens or even hundreds of free parameters. Emerging high-throughput experimental strategies such as the one employed here provide fundamentally new information that has the potential to transform the sensitivity of phylogenetic and genetic analyses.",-1),l=[s,i];function m(d,c,p,h,u,g){return o(),a("div",null,l)}const y=t(r,[["render",m]]);export{f as __pageData,y as default}; diff --git a/assets/papers_2014_gong.md.DMPvmYKy.js b/assets/papers_2014_gong.md.D6j_RWFK.js similarity index 97% rename from assets/papers_2014_gong.md.DMPvmYKy.js rename to assets/papers_2014_gong.md.D6j_RWFK.js index 34c677b..dc58a9a 100644 --- a/assets/papers_2014_gong.md.DMPvmYKy.js +++ b/assets/papers_2014_gong.md.D6j_RWFK.js @@ -1 +1 @@ -import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const y=JSON.parse('{"title":"Epistatically interacting substitutions are enriched during adaptive protein evolution","description":"","frontmatter":{"layout":"paper","title":"Epistatically interacting substitutions are enriched during adaptive protein evolution","date":"2014-05-08","authors":["Lizhi Ian Gong","Jesse D Bloom"],"journal":"PLoS genetics","doi":"10.1371/journal.pgen.1004328","link":"https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004328","image":"/assets/papers/2014_gong.png","keywords":["Influenza","Epistasis"]},"headers":[],"relativePath":"papers/2014_gong.md","filePath":"papers/2014_gong.md"}'),o={name:"papers/2014_gong.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Most experimental studies of epistasis in evolution have focused on adaptive changes—but adaptation accounts for only a portion of total evolutionary change. Are the patterns of epistasis during adaptation representative of evolution more broadly? We address this question by examining a pair of protein homologs, of which only one is subject to a well-defined pressure for adaptive change. Specifically, we compare the nucleoproteins from human and swine influenza. Human influenza is under continual selection to evade recognition by acquired immune memory, while swine influenza experiences less such selection due to the fact that pigs are less likely to be infected with influenza repeatedly in a lifetime. Mutations in some types of immune epitopes are therefore much more strongly adaptive to human than swine influenza—here we focus on epitopes targeted by human cytotoxic T lymphocytes. The nucleoproteins of human and swine influenza possess nearly identical numbers of such epitopes. However, mutations in these epitopes are fixed significantly more frequently in human than in swine influenza, presumably because these epitope mutations are adaptive only to human influenza. Experimentally, we find that epistatically constrained mutations are fixed only in the adaptively evolving human influenza lineage, where they occur at sites that are enriched in epitopes. Overall, our results demonstrate that epistatically interacting substitutions are enriched during adaptation, suggesting that the prevalence of epistasis is dependent on the underlying evolutionary forces at play.",-1),l=[s,r];function p(u,c,d,h,f,m){return n(),a("div",null,l)}const v=t(o,[["render",p]]);export{y as __pageData,v as default}; +import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const y=JSON.parse('{"title":"Epistatically interacting substitutions are enriched during adaptive protein evolution","description":"","frontmatter":{"layout":"paper","title":"Epistatically interacting substitutions are enriched during adaptive protein evolution","date":"2014-05-08","authors":["Lizhi Ian Gong","Jesse D Bloom"],"journal":"PLoS genetics","doi":"10.1371/journal.pgen.1004328","link":"https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004328","image":"/assets/papers/2014_gong.png","keywords":["Influenza","Epistasis"]},"headers":[],"relativePath":"papers/2014_gong.md","filePath":"papers/2014_gong.md"}'),o={name:"papers/2014_gong.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Most experimental studies of epistasis in evolution have focused on adaptive changes—but adaptation accounts for only a portion of total evolutionary change. Are the patterns of epistasis during adaptation representative of evolution more broadly? We address this question by examining a pair of protein homologs, of which only one is subject to a well-defined pressure for adaptive change. Specifically, we compare the nucleoproteins from human and swine influenza. Human influenza is under continual selection to evade recognition by acquired immune memory, while swine influenza experiences less such selection due to the fact that pigs are less likely to be infected with influenza repeatedly in a lifetime. Mutations in some types of immune epitopes are therefore much more strongly adaptive to human than swine influenza—here we focus on epitopes targeted by human cytotoxic T lymphocytes. The nucleoproteins of human and swine influenza possess nearly identical numbers of such epitopes. However, mutations in these epitopes are fixed significantly more frequently in human than in swine influenza, presumably because these epitope mutations are adaptive only to human influenza. Experimentally, we find that epistatically constrained mutations are fixed only in the adaptively evolving human influenza lineage, where they occur at sites that are enriched in epitopes. Overall, our results demonstrate that epistatically interacting substitutions are enriched during adaptation, suggesting that the prevalence of epistasis is dependent on the underlying evolutionary forces at play.",-1),l=[s,r];function p(u,c,d,h,f,m){return n(),a("div",null,l)}const v=t(o,[["render",p]]);export{y as __pageData,v as default}; diff --git a/assets/papers_2014_gong.md.DMPvmYKy.lean.js b/assets/papers_2014_gong.md.D6j_RWFK.lean.js similarity index 97% rename from assets/papers_2014_gong.md.DMPvmYKy.lean.js rename to assets/papers_2014_gong.md.D6j_RWFK.lean.js index 34c677b..dc58a9a 100644 --- a/assets/papers_2014_gong.md.DMPvmYKy.lean.js +++ b/assets/papers_2014_gong.md.D6j_RWFK.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const y=JSON.parse('{"title":"Epistatically interacting substitutions are enriched during adaptive protein evolution","description":"","frontmatter":{"layout":"paper","title":"Epistatically interacting substitutions are enriched during adaptive protein evolution","date":"2014-05-08","authors":["Lizhi Ian Gong","Jesse D Bloom"],"journal":"PLoS genetics","doi":"10.1371/journal.pgen.1004328","link":"https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004328","image":"/assets/papers/2014_gong.png","keywords":["Influenza","Epistasis"]},"headers":[],"relativePath":"papers/2014_gong.md","filePath":"papers/2014_gong.md"}'),o={name:"papers/2014_gong.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Most experimental studies of epistasis in evolution have focused on adaptive changes—but adaptation accounts for only a portion of total evolutionary change. Are the patterns of epistasis during adaptation representative of evolution more broadly? We address this question by examining a pair of protein homologs, of which only one is subject to a well-defined pressure for adaptive change. Specifically, we compare the nucleoproteins from human and swine influenza. Human influenza is under continual selection to evade recognition by acquired immune memory, while swine influenza experiences less such selection due to the fact that pigs are less likely to be infected with influenza repeatedly in a lifetime. Mutations in some types of immune epitopes are therefore much more strongly adaptive to human than swine influenza—here we focus on epitopes targeted by human cytotoxic T lymphocytes. The nucleoproteins of human and swine influenza possess nearly identical numbers of such epitopes. However, mutations in these epitopes are fixed significantly more frequently in human than in swine influenza, presumably because these epitope mutations are adaptive only to human influenza. Experimentally, we find that epistatically constrained mutations are fixed only in the adaptively evolving human influenza lineage, where they occur at sites that are enriched in epitopes. Overall, our results demonstrate that epistatically interacting substitutions are enriched during adaptation, suggesting that the prevalence of epistasis is dependent on the underlying evolutionary forces at play.",-1),l=[s,r];function p(u,c,d,h,f,m){return n(),a("div",null,l)}const v=t(o,[["render",p]]);export{y as __pageData,v as default}; +import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const y=JSON.parse('{"title":"Epistatically interacting substitutions are enriched during adaptive protein evolution","description":"","frontmatter":{"layout":"paper","title":"Epistatically interacting substitutions are enriched during adaptive protein evolution","date":"2014-05-08","authors":["Lizhi Ian Gong","Jesse D Bloom"],"journal":"PLoS genetics","doi":"10.1371/journal.pgen.1004328","link":"https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004328","image":"/assets/papers/2014_gong.png","keywords":["Influenza","Epistasis"]},"headers":[],"relativePath":"papers/2014_gong.md","filePath":"papers/2014_gong.md"}'),o={name:"papers/2014_gong.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Most experimental studies of epistasis in evolution have focused on adaptive changes—but adaptation accounts for only a portion of total evolutionary change. Are the patterns of epistasis during adaptation representative of evolution more broadly? We address this question by examining a pair of protein homologs, of which only one is subject to a well-defined pressure for adaptive change. Specifically, we compare the nucleoproteins from human and swine influenza. Human influenza is under continual selection to evade recognition by acquired immune memory, while swine influenza experiences less such selection due to the fact that pigs are less likely to be infected with influenza repeatedly in a lifetime. Mutations in some types of immune epitopes are therefore much more strongly adaptive to human than swine influenza—here we focus on epitopes targeted by human cytotoxic T lymphocytes. The nucleoproteins of human and swine influenza possess nearly identical numbers of such epitopes. However, mutations in these epitopes are fixed significantly more frequently in human than in swine influenza, presumably because these epitope mutations are adaptive only to human influenza. Experimentally, we find that epistatically constrained mutations are fixed only in the adaptively evolving human influenza lineage, where they occur at sites that are enriched in epitopes. Overall, our results demonstrate that epistatically interacting substitutions are enriched during adaptation, suggesting that the prevalence of epistasis is dependent on the underlying evolutionary forces at play.",-1),l=[s,r];function p(u,c,d,h,f,m){return n(),a("div",null,l)}const v=t(o,[["render",p]]);export{y as __pageData,v as default}; diff --git a/assets/papers_2014_thyagarajan.md.Dsn4JUlI.js b/assets/papers_2014_thyagarajan.md.Dx5eh_Ub.js similarity index 96% rename from assets/papers_2014_thyagarajan.md.Dsn4JUlI.js rename to assets/papers_2014_thyagarajan.md.Dx5eh_Ub.js index dcf5a22..b597057 100644 --- a/assets/papers_2014_thyagarajan.md.Dsn4JUlI.js +++ b/assets/papers_2014_thyagarajan.md.Dx5eh_Ub.js @@ -1 +1 @@ -import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin","date":"2014-07-08","authors":["Bargavi Thyagarajan","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.03300","link":"https://elifesciences.org/articles/3300","image":"/assets/papers/2014_thyagarajan.jpg","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2014_thyagarajan.md","filePath":"papers/2014_thyagarajan.md"}'),s={name:"papers/2014_thyagarajan.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza is notable for its evolutionary capacity to escape immunity targeting the viral hemagglutinin. We used deep mutational scanning to examine the extent to which a high inherent mutational tolerance contributes to this antigenic evolvability. We created mutant viruses that incorporate most of the ≈104 amino-acid mutations to hemagglutinin from A/WSN/1933 (H1N1) influenza. After passaging these viruses in tissue culture to select for functional variants, we used deep sequencing to quantify mutation frequencies before and after selection. These data enable us to infer the preference for each amino acid at each site in hemagglutinin. These inferences are consistent with existing knowledge about the protein's structure and function, and can be used to create a model that describes hemagglutinin's evolution far better than existing phylogenetic models. We show that hemagglutinin has a high inherent tolerance for mutations at antigenic sites, suggesting that this is one factor contributing to influenza's antigenic evolution.",-1),c=[o,r];function l(h,u,g,d,f,m){return n(),a("div",null,c)}const b=t(s,[["render",l]]);export{_ as __pageData,b as default}; +import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin","date":"2014-07-08","authors":["Bargavi Thyagarajan","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.03300","link":"https://elifesciences.org/articles/3300","image":"/assets/papers/2014_thyagarajan.jpg","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2014_thyagarajan.md","filePath":"papers/2014_thyagarajan.md"}'),s={name:"papers/2014_thyagarajan.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza is notable for its evolutionary capacity to escape immunity targeting the viral hemagglutinin. We used deep mutational scanning to examine the extent to which a high inherent mutational tolerance contributes to this antigenic evolvability. We created mutant viruses that incorporate most of the ≈104 amino-acid mutations to hemagglutinin from A/WSN/1933 (H1N1) influenza. After passaging these viruses in tissue culture to select for functional variants, we used deep sequencing to quantify mutation frequencies before and after selection. These data enable us to infer the preference for each amino acid at each site in hemagglutinin. These inferences are consistent with existing knowledge about the protein's structure and function, and can be used to create a model that describes hemagglutinin's evolution far better than existing phylogenetic models. We show that hemagglutinin has a high inherent tolerance for mutations at antigenic sites, suggesting that this is one factor contributing to influenza's antigenic evolution.",-1),c=[o,r];function l(h,u,g,d,f,m){return n(),a("div",null,c)}const b=t(s,[["render",l]]);export{_ as __pageData,b as default}; diff --git a/assets/papers_2014_thyagarajan.md.Dsn4JUlI.lean.js b/assets/papers_2014_thyagarajan.md.Dx5eh_Ub.lean.js similarity index 96% rename from assets/papers_2014_thyagarajan.md.Dsn4JUlI.lean.js rename to assets/papers_2014_thyagarajan.md.Dx5eh_Ub.lean.js index dcf5a22..b597057 100644 --- a/assets/papers_2014_thyagarajan.md.Dsn4JUlI.lean.js +++ b/assets/papers_2014_thyagarajan.md.Dx5eh_Ub.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin","date":"2014-07-08","authors":["Bargavi Thyagarajan","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.03300","link":"https://elifesciences.org/articles/3300","image":"/assets/papers/2014_thyagarajan.jpg","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2014_thyagarajan.md","filePath":"papers/2014_thyagarajan.md"}'),s={name:"papers/2014_thyagarajan.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza is notable for its evolutionary capacity to escape immunity targeting the viral hemagglutinin. We used deep mutational scanning to examine the extent to which a high inherent mutational tolerance contributes to this antigenic evolvability. We created mutant viruses that incorporate most of the ≈104 amino-acid mutations to hemagglutinin from A/WSN/1933 (H1N1) influenza. After passaging these viruses in tissue culture to select for functional variants, we used deep sequencing to quantify mutation frequencies before and after selection. These data enable us to infer the preference for each amino acid at each site in hemagglutinin. These inferences are consistent with existing knowledge about the protein's structure and function, and can be used to create a model that describes hemagglutinin's evolution far better than existing phylogenetic models. We show that hemagglutinin has a high inherent tolerance for mutations at antigenic sites, suggesting that this is one factor contributing to influenza's antigenic evolution.",-1),c=[o,r];function l(h,u,g,d,f,m){return n(),a("div",null,c)}const b=t(s,[["render",l]]);export{_ as __pageData,b as default}; +import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin","date":"2014-07-08","authors":["Bargavi Thyagarajan","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.03300","link":"https://elifesciences.org/articles/3300","image":"/assets/papers/2014_thyagarajan.jpg","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2014_thyagarajan.md","filePath":"papers/2014_thyagarajan.md"}'),s={name:"papers/2014_thyagarajan.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza is notable for its evolutionary capacity to escape immunity targeting the viral hemagglutinin. We used deep mutational scanning to examine the extent to which a high inherent mutational tolerance contributes to this antigenic evolvability. We created mutant viruses that incorporate most of the ≈104 amino-acid mutations to hemagglutinin from A/WSN/1933 (H1N1) influenza. After passaging these viruses in tissue culture to select for functional variants, we used deep sequencing to quantify mutation frequencies before and after selection. These data enable us to infer the preference for each amino acid at each site in hemagglutinin. These inferences are consistent with existing knowledge about the protein's structure and function, and can be used to create a model that describes hemagglutinin's evolution far better than existing phylogenetic models. We show that hemagglutinin has a high inherent tolerance for mutations at antigenic sites, suggesting that this is one factor contributing to influenza's antigenic evolution.",-1),c=[o,r];function l(h,u,g,d,f,m){return n(),a("div",null,c)}const b=t(s,[["render",l]]);export{_ as __pageData,b as default}; diff --git a/assets/papers_2015_bloom.md.CzMV_7-e.js b/assets/papers_2015_bloom.md.D3hHe5R3.js similarity index 96% rename from assets/papers_2015_bloom.md.CzMV_7-e.js rename to assets/papers_2015_bloom.md.D3hHe5R3.js index 7d7a3f0..86bace2 100644 --- a/assets/papers_2015_bloom.md.CzMV_7-e.js +++ b/assets/papers_2015_bloom.md.D3hHe5R3.js @@ -1 +1 @@ -import{_ as t,c as a,o as s,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Software for the analysis and visualization of deep mutational scanning data","description":"","frontmatter":{"layout":"paper","title":"Software for the analysis and visualization of deep mutational scanning data","date":"2015-12-01","authors":["Jesse D Bloom"],"journal":"BMC bioinformatics","doi":"10.1186/s12859-015-0590-4","link":"https://link.springer.com/article/10.1186/s12859-015-0590-4","image":"/assets/papers/2015_bloom.jpg","keywords":["Software tools"]},"headers":[],"relativePath":"papers/2015_bloom.md","filePath":"papers/2015_bloom.md"}'),n={name:"papers/2015_bloom.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Deep mutational scanning is a technique to estimate the impacts of mutations on a gene by using deep sequencing to count mutations in a library of variants before and after imposing a functional selection. The impacts of mutations must be inferred from changes in their counts after selection.",-1),c=e("p",null,"I describe a software package, dms_tools, to infer the impacts of mutations from deep mutational scanning data using a likelihood-based treatment of the mutation counts. I show that dms_tools yields more accurate inferences on simulated data than simply calculating ratios of counts pre- and post-selection. Using dms_tools, one can infer the preference of each site for each amino acid given a single selection pressure, or assess the extent to which these preferences change under different selection pressures.",-1),l=[i,r,c];function d(m,p,f,u,h,_){return s(),a("div",null,l)}const k=t(n,[["render",d]]);export{b as __pageData,k as default}; +import{_ as t,c as a,o as s,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Software for the analysis and visualization of deep mutational scanning data","description":"","frontmatter":{"layout":"paper","title":"Software for the analysis and visualization of deep mutational scanning data","date":"2015-12-01","authors":["Jesse D Bloom"],"journal":"BMC bioinformatics","doi":"10.1186/s12859-015-0590-4","link":"https://link.springer.com/article/10.1186/s12859-015-0590-4","image":"/assets/papers/2015_bloom.jpg","keywords":["Software tools"]},"headers":[],"relativePath":"papers/2015_bloom.md","filePath":"papers/2015_bloom.md"}'),n={name:"papers/2015_bloom.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Deep mutational scanning is a technique to estimate the impacts of mutations on a gene by using deep sequencing to count mutations in a library of variants before and after imposing a functional selection. The impacts of mutations must be inferred from changes in their counts after selection.",-1),c=e("p",null,"I describe a software package, dms_tools, to infer the impacts of mutations from deep mutational scanning data using a likelihood-based treatment of the mutation counts. I show that dms_tools yields more accurate inferences on simulated data than simply calculating ratios of counts pre- and post-selection. Using dms_tools, one can infer the preference of each site for each amino acid given a single selection pressure, or assess the extent to which these preferences change under different selection pressures.",-1),l=[i,r,c];function d(m,p,f,u,h,_){return s(),a("div",null,l)}const k=t(n,[["render",d]]);export{b as __pageData,k as default}; diff --git a/assets/papers_2015_bloom.md.CzMV_7-e.lean.js b/assets/papers_2015_bloom.md.D3hHe5R3.lean.js similarity index 96% rename from assets/papers_2015_bloom.md.CzMV_7-e.lean.js rename to assets/papers_2015_bloom.md.D3hHe5R3.lean.js index 7d7a3f0..86bace2 100644 --- a/assets/papers_2015_bloom.md.CzMV_7-e.lean.js +++ b/assets/papers_2015_bloom.md.D3hHe5R3.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as s,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Software for the analysis and visualization of deep mutational scanning data","description":"","frontmatter":{"layout":"paper","title":"Software for the analysis and visualization of deep mutational scanning data","date":"2015-12-01","authors":["Jesse D Bloom"],"journal":"BMC bioinformatics","doi":"10.1186/s12859-015-0590-4","link":"https://link.springer.com/article/10.1186/s12859-015-0590-4","image":"/assets/papers/2015_bloom.jpg","keywords":["Software tools"]},"headers":[],"relativePath":"papers/2015_bloom.md","filePath":"papers/2015_bloom.md"}'),n={name:"papers/2015_bloom.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Deep mutational scanning is a technique to estimate the impacts of mutations on a gene by using deep sequencing to count mutations in a library of variants before and after imposing a functional selection. The impacts of mutations must be inferred from changes in their counts after selection.",-1),c=e("p",null,"I describe a software package, dms_tools, to infer the impacts of mutations from deep mutational scanning data using a likelihood-based treatment of the mutation counts. I show that dms_tools yields more accurate inferences on simulated data than simply calculating ratios of counts pre- and post-selection. Using dms_tools, one can infer the preference of each site for each amino acid given a single selection pressure, or assess the extent to which these preferences change under different selection pressures.",-1),l=[i,r,c];function d(m,p,f,u,h,_){return s(),a("div",null,l)}const k=t(n,[["render",d]]);export{b as __pageData,k as default}; +import{_ as t,c as a,o as s,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Software for the analysis and visualization of deep mutational scanning data","description":"","frontmatter":{"layout":"paper","title":"Software for the analysis and visualization of deep mutational scanning data","date":"2015-12-01","authors":["Jesse D Bloom"],"journal":"BMC bioinformatics","doi":"10.1186/s12859-015-0590-4","link":"https://link.springer.com/article/10.1186/s12859-015-0590-4","image":"/assets/papers/2015_bloom.jpg","keywords":["Software tools"]},"headers":[],"relativePath":"papers/2015_bloom.md","filePath":"papers/2015_bloom.md"}'),n={name:"papers/2015_bloom.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Deep mutational scanning is a technique to estimate the impacts of mutations on a gene by using deep sequencing to count mutations in a library of variants before and after imposing a functional selection. The impacts of mutations must be inferred from changes in their counts after selection.",-1),c=e("p",null,"I describe a software package, dms_tools, to infer the impacts of mutations from deep mutational scanning data using a likelihood-based treatment of the mutation counts. I show that dms_tools yields more accurate inferences on simulated data than simply calculating ratios of counts pre- and post-selection. Using dms_tools, one can infer the preference of each site for each amino acid given a single selection pressure, or assess the extent to which these preferences change under different selection pressures.",-1),l=[i,r,c];function d(m,p,f,u,h,_){return s(),a("div",null,l)}const k=t(n,[["render",d]]);export{b as __pageData,k as default}; diff --git a/assets/papers_2015_doud.md.4Lv_UQBS.js b/assets/papers_2015_doud.md.48Gi8XhC.js similarity index 97% rename from assets/papers_2015_doud.md.4Lv_UQBS.js rename to assets/papers_2015_doud.md.48Gi8XhC.js index 1d8682f..57aea04 100644 --- a/assets/papers_2015_doud.md.4Lv_UQBS.js +++ b/assets/papers_2015_doud.md.48Gi8XhC.js @@ -1 +1 @@ -import{_ as t,c as o,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const v=JSON.parse('{"title":"Site-specific amino acid preferences are mostly conserved in two closely related protein homologs","description":"","frontmatter":{"layout":"paper","title":"Site-specific amino acid preferences are mostly conserved in two closely related protein homologs","date":"2015-11-01","authors":["Michael B Doud","Orr Ashenberg","Jesse D Bloom"],"journal":"Molecular biology and evolution","doi":"10.1093/molbev/msv167","link":"https://academic.oup.com/mbe/article/32/11/2944/982113","image":"/assets/papers/2015_doud.jpg","keywords":["Influenza","Epistasis","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2015_doud.md","filePath":"papers/2015_doud.md"}'),a={name:"papers/2015_doud.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Evolution drives changes in a protein’s sequence over time. The extent to which these changes in sequence lead to shifts in the underlying preference for each amino acid at each site is an important question with implications for comparative sequence-analysis methods, such as molecular phylogenetics. To quantify the extent that site-specific amino acid preferences shift during evolution, we performed deep mutational scanning on two homologs of human influenza nucleoprotein with 94% amino acid identity. We found that only a modest fraction of sites exhibited shifts in amino acid preferences that exceeded the noise in our experiments. Furthermore, even among sites that did exhibit detectable shifts, the magnitude tended to be small relative to differences between nonhomologous proteins. Given the limited change in amino acid preferences between these close homologs, we tested whether our measurements could inform site-specific substitution models that describe the evolution of nucleoproteins from more diverse influenza viruses. We found that site-specific evolutionary models informed by our experiments greatly outperformed nonsite-specific alternatives in fitting phylogenies of nucleoproteins from human, swine, equine, and avian influenza. Combining the experimental data from both homologs improved phylogenetic fit, partly because measurements in multiple genetic contexts better captured the evolutionary average of the amino acid preferences for sites with shifting preferences. Our results show that site-specific amino acid preferences are sufficiently conserved that measuring mutational effects in one protein provides information that can improve quantitative evolutionary modeling of nearby homologs.",-1),c=[s,r];function l(d,m,h,p,u,f){return i(),o("div",null,c)}const b=t(a,[["render",l]]);export{v as __pageData,b as default}; +import{_ as t,c as o,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const v=JSON.parse('{"title":"Site-specific amino acid preferences are mostly conserved in two closely related protein homologs","description":"","frontmatter":{"layout":"paper","title":"Site-specific amino acid preferences are mostly conserved in two closely related protein homologs","date":"2015-11-01","authors":["Michael B Doud","Orr Ashenberg","Jesse D Bloom"],"journal":"Molecular biology and evolution","doi":"10.1093/molbev/msv167","link":"https://academic.oup.com/mbe/article/32/11/2944/982113","image":"/assets/papers/2015_doud.jpg","keywords":["Influenza","Epistasis","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2015_doud.md","filePath":"papers/2015_doud.md"}'),a={name:"papers/2015_doud.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Evolution drives changes in a protein’s sequence over time. The extent to which these changes in sequence lead to shifts in the underlying preference for each amino acid at each site is an important question with implications for comparative sequence-analysis methods, such as molecular phylogenetics. To quantify the extent that site-specific amino acid preferences shift during evolution, we performed deep mutational scanning on two homologs of human influenza nucleoprotein with 94% amino acid identity. We found that only a modest fraction of sites exhibited shifts in amino acid preferences that exceeded the noise in our experiments. Furthermore, even among sites that did exhibit detectable shifts, the magnitude tended to be small relative to differences between nonhomologous proteins. Given the limited change in amino acid preferences between these close homologs, we tested whether our measurements could inform site-specific substitution models that describe the evolution of nucleoproteins from more diverse influenza viruses. We found that site-specific evolutionary models informed by our experiments greatly outperformed nonsite-specific alternatives in fitting phylogenies of nucleoproteins from human, swine, equine, and avian influenza. Combining the experimental data from both homologs improved phylogenetic fit, partly because measurements in multiple genetic contexts better captured the evolutionary average of the amino acid preferences for sites with shifting preferences. Our results show that site-specific amino acid preferences are sufficiently conserved that measuring mutational effects in one protein provides information that can improve quantitative evolutionary modeling of nearby homologs.",-1),c=[s,r];function l(d,m,h,p,u,f){return i(),o("div",null,c)}const b=t(a,[["render",l]]);export{v as __pageData,b as default}; diff --git a/assets/papers_2015_doud.md.4Lv_UQBS.lean.js b/assets/papers_2015_doud.md.48Gi8XhC.lean.js similarity index 97% rename from assets/papers_2015_doud.md.4Lv_UQBS.lean.js rename to assets/papers_2015_doud.md.48Gi8XhC.lean.js index 1d8682f..57aea04 100644 --- a/assets/papers_2015_doud.md.4Lv_UQBS.lean.js +++ b/assets/papers_2015_doud.md.48Gi8XhC.lean.js @@ -1 +1 @@ -import{_ as t,c as o,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const v=JSON.parse('{"title":"Site-specific amino acid preferences are mostly conserved in two closely related protein homologs","description":"","frontmatter":{"layout":"paper","title":"Site-specific amino acid preferences are mostly conserved in two closely related protein homologs","date":"2015-11-01","authors":["Michael B Doud","Orr Ashenberg","Jesse D Bloom"],"journal":"Molecular biology and evolution","doi":"10.1093/molbev/msv167","link":"https://academic.oup.com/mbe/article/32/11/2944/982113","image":"/assets/papers/2015_doud.jpg","keywords":["Influenza","Epistasis","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2015_doud.md","filePath":"papers/2015_doud.md"}'),a={name:"papers/2015_doud.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Evolution drives changes in a protein’s sequence over time. The extent to which these changes in sequence lead to shifts in the underlying preference for each amino acid at each site is an important question with implications for comparative sequence-analysis methods, such as molecular phylogenetics. To quantify the extent that site-specific amino acid preferences shift during evolution, we performed deep mutational scanning on two homologs of human influenza nucleoprotein with 94% amino acid identity. We found that only a modest fraction of sites exhibited shifts in amino acid preferences that exceeded the noise in our experiments. Furthermore, even among sites that did exhibit detectable shifts, the magnitude tended to be small relative to differences between nonhomologous proteins. Given the limited change in amino acid preferences between these close homologs, we tested whether our measurements could inform site-specific substitution models that describe the evolution of nucleoproteins from more diverse influenza viruses. We found that site-specific evolutionary models informed by our experiments greatly outperformed nonsite-specific alternatives in fitting phylogenies of nucleoproteins from human, swine, equine, and avian influenza. Combining the experimental data from both homologs improved phylogenetic fit, partly because measurements in multiple genetic contexts better captured the evolutionary average of the amino acid preferences for sites with shifting preferences. Our results show that site-specific amino acid preferences are sufficiently conserved that measuring mutational effects in one protein provides information that can improve quantitative evolutionary modeling of nearby homologs.",-1),c=[s,r];function l(d,m,h,p,u,f){return i(),o("div",null,c)}const b=t(a,[["render",l]]);export{v as __pageData,b as default}; +import{_ as t,c as o,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const v=JSON.parse('{"title":"Site-specific amino acid preferences are mostly conserved in two closely related protein homologs","description":"","frontmatter":{"layout":"paper","title":"Site-specific amino acid preferences are mostly conserved in two closely related protein homologs","date":"2015-11-01","authors":["Michael B Doud","Orr Ashenberg","Jesse D Bloom"],"journal":"Molecular biology and evolution","doi":"10.1093/molbev/msv167","link":"https://academic.oup.com/mbe/article/32/11/2944/982113","image":"/assets/papers/2015_doud.jpg","keywords":["Influenza","Epistasis","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2015_doud.md","filePath":"papers/2015_doud.md"}'),a={name:"papers/2015_doud.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Evolution drives changes in a protein’s sequence over time. The extent to which these changes in sequence lead to shifts in the underlying preference for each amino acid at each site is an important question with implications for comparative sequence-analysis methods, such as molecular phylogenetics. To quantify the extent that site-specific amino acid preferences shift during evolution, we performed deep mutational scanning on two homologs of human influenza nucleoprotein with 94% amino acid identity. We found that only a modest fraction of sites exhibited shifts in amino acid preferences that exceeded the noise in our experiments. Furthermore, even among sites that did exhibit detectable shifts, the magnitude tended to be small relative to differences between nonhomologous proteins. Given the limited change in amino acid preferences between these close homologs, we tested whether our measurements could inform site-specific substitution models that describe the evolution of nucleoproteins from more diverse influenza viruses. We found that site-specific evolutionary models informed by our experiments greatly outperformed nonsite-specific alternatives in fitting phylogenies of nucleoproteins from human, swine, equine, and avian influenza. Combining the experimental data from both homologs improved phylogenetic fit, partly because measurements in multiple genetic contexts better captured the evolutionary average of the amino acid preferences for sites with shifting preferences. Our results show that site-specific amino acid preferences are sufficiently conserved that measuring mutational effects in one protein provides information that can improve quantitative evolutionary modeling of nearby homologs.",-1),c=[s,r];function l(d,m,h,p,u,f){return i(),o("div",null,c)}const b=t(a,[["render",l]]);export{v as __pageData,b as default}; diff --git a/assets/papers_2015_hooper.md.D3y9DeY5.js b/assets/papers_2015_hooper.md.CI0Ar8ga.js similarity index 97% rename from assets/papers_2015_hooper.md.D3y9DeY5.js rename to assets/papers_2015_hooper.md.CI0Ar8ga.js index 201d2ec..71e6849 100644 --- a/assets/papers_2015_hooper.md.D3y9DeY5.js +++ b/assets/papers_2015_hooper.md.CI0Ar8ga.js @@ -1 +1 @@ -import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const v=JSON.parse('{"title":"Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice","description":"","frontmatter":{"layout":"paper","title":"Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice","date":"2015-04-01","authors":["Kathryn A Hooper","James E Crowe Jr","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.00012-15","link":"https://journals.asm.org/doi/full/10.1128/jvi.00012-15","image":"/assets/papers/2015_hooper.jpg","keywords":["Influenza"]},"headers":[],"relativePath":"papers/2015_hooper.md","filePath":"papers/2015_hooper.md"}'),r={name:"papers/2015_hooper.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"In nearly all characterized influenza viruses, hemagglutinin (HA) is the receptor-binding protein while neuraminidase (NA) is a receptor-cleaving protein that aids in viral release. However, in recent years, several groups have described point mutations that confer receptor-binding activity on NA, albeit in laboratory rather than natural settings. One of these mutations, D151G, appears to arise in the NA of recent human H3N2 viruses upon passage in tissue culture. We inadvertently isolated the second of these mutations, G147R, in the NA of the lab-adapted A/WSN/33 (H1N1) strain while we were passaging a heavily engineered virus in the lab. G147R also occurs at low frequencies in the reported sequences of viruses from three different lineages: human 2009 pandemic H1N1 (pdmH1N1), human seasonal H1N1, and chicken H5N1. Here we reconstructed a representative G147R NA from each of these lineages and found that all of the proteins have acquired the ability to bind an unknown cellular receptor while retaining substantial sialidase activity. We then reconstructed a virus with the HA and NA of a reported G147R pdmH1N1 variant and found no attenuation of viral replication in cell culture or change in pathogenesis in mice. Furthermore, the G147R virus had modestly enhanced resistance to neutralization by the Fab of an antibody against the receptor-binding pocket of HA, although it remained completely sensitive to the full-length IgG. Overall, our results suggest that circulating N1 viruses occasionally may acquire the G147R NA receptor-binding mutation without impairment of replicative capacity.",-1),l=[o,s];function c(u,h,d,p,m,f){return n(),t("div",null,l)}const b=a(r,[["render",c]]);export{v as __pageData,b as default}; +import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const v=JSON.parse('{"title":"Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice","description":"","frontmatter":{"layout":"paper","title":"Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice","date":"2015-04-01","authors":["Kathryn A Hooper","James E Crowe Jr","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.00012-15","link":"https://journals.asm.org/doi/full/10.1128/jvi.00012-15","image":"/assets/papers/2015_hooper.jpg","keywords":["Influenza"]},"headers":[],"relativePath":"papers/2015_hooper.md","filePath":"papers/2015_hooper.md"}'),r={name:"papers/2015_hooper.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"In nearly all characterized influenza viruses, hemagglutinin (HA) is the receptor-binding protein while neuraminidase (NA) is a receptor-cleaving protein that aids in viral release. However, in recent years, several groups have described point mutations that confer receptor-binding activity on NA, albeit in laboratory rather than natural settings. One of these mutations, D151G, appears to arise in the NA of recent human H3N2 viruses upon passage in tissue culture. We inadvertently isolated the second of these mutations, G147R, in the NA of the lab-adapted A/WSN/33 (H1N1) strain while we were passaging a heavily engineered virus in the lab. G147R also occurs at low frequencies in the reported sequences of viruses from three different lineages: human 2009 pandemic H1N1 (pdmH1N1), human seasonal H1N1, and chicken H5N1. Here we reconstructed a representative G147R NA from each of these lineages and found that all of the proteins have acquired the ability to bind an unknown cellular receptor while retaining substantial sialidase activity. We then reconstructed a virus with the HA and NA of a reported G147R pdmH1N1 variant and found no attenuation of viral replication in cell culture or change in pathogenesis in mice. Furthermore, the G147R virus had modestly enhanced resistance to neutralization by the Fab of an antibody against the receptor-binding pocket of HA, although it remained completely sensitive to the full-length IgG. Overall, our results suggest that circulating N1 viruses occasionally may acquire the G147R NA receptor-binding mutation without impairment of replicative capacity.",-1),l=[o,s];function c(u,h,d,p,m,f){return n(),t("div",null,l)}const b=a(r,[["render",c]]);export{v as __pageData,b as default}; diff --git a/assets/papers_2015_hooper.md.D3y9DeY5.lean.js b/assets/papers_2015_hooper.md.CI0Ar8ga.lean.js similarity index 97% rename from assets/papers_2015_hooper.md.D3y9DeY5.lean.js rename to assets/papers_2015_hooper.md.CI0Ar8ga.lean.js index 201d2ec..71e6849 100644 --- a/assets/papers_2015_hooper.md.D3y9DeY5.lean.js +++ b/assets/papers_2015_hooper.md.CI0Ar8ga.lean.js @@ -1 +1 @@ -import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const v=JSON.parse('{"title":"Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice","description":"","frontmatter":{"layout":"paper","title":"Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice","date":"2015-04-01","authors":["Kathryn A Hooper","James E Crowe Jr","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.00012-15","link":"https://journals.asm.org/doi/full/10.1128/jvi.00012-15","image":"/assets/papers/2015_hooper.jpg","keywords":["Influenza"]},"headers":[],"relativePath":"papers/2015_hooper.md","filePath":"papers/2015_hooper.md"}'),r={name:"papers/2015_hooper.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"In nearly all characterized influenza viruses, hemagglutinin (HA) is the receptor-binding protein while neuraminidase (NA) is a receptor-cleaving protein that aids in viral release. However, in recent years, several groups have described point mutations that confer receptor-binding activity on NA, albeit in laboratory rather than natural settings. One of these mutations, D151G, appears to arise in the NA of recent human H3N2 viruses upon passage in tissue culture. We inadvertently isolated the second of these mutations, G147R, in the NA of the lab-adapted A/WSN/33 (H1N1) strain while we were passaging a heavily engineered virus in the lab. G147R also occurs at low frequencies in the reported sequences of viruses from three different lineages: human 2009 pandemic H1N1 (pdmH1N1), human seasonal H1N1, and chicken H5N1. Here we reconstructed a representative G147R NA from each of these lineages and found that all of the proteins have acquired the ability to bind an unknown cellular receptor while retaining substantial sialidase activity. We then reconstructed a virus with the HA and NA of a reported G147R pdmH1N1 variant and found no attenuation of viral replication in cell culture or change in pathogenesis in mice. Furthermore, the G147R virus had modestly enhanced resistance to neutralization by the Fab of an antibody against the receptor-binding pocket of HA, although it remained completely sensitive to the full-length IgG. Overall, our results suggest that circulating N1 viruses occasionally may acquire the G147R NA receptor-binding mutation without impairment of replicative capacity.",-1),l=[o,s];function c(u,h,d,p,m,f){return n(),t("div",null,l)}const b=a(r,[["render",c]]);export{v as __pageData,b as default}; +import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const v=JSON.parse('{"title":"Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice","description":"","frontmatter":{"layout":"paper","title":"Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice","date":"2015-04-01","authors":["Kathryn A Hooper","James E Crowe Jr","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.00012-15","link":"https://journals.asm.org/doi/full/10.1128/jvi.00012-15","image":"/assets/papers/2015_hooper.jpg","keywords":["Influenza"]},"headers":[],"relativePath":"papers/2015_hooper.md","filePath":"papers/2015_hooper.md"}'),r={name:"papers/2015_hooper.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"In nearly all characterized influenza viruses, hemagglutinin (HA) is the receptor-binding protein while neuraminidase (NA) is a receptor-cleaving protein that aids in viral release. However, in recent years, several groups have described point mutations that confer receptor-binding activity on NA, albeit in laboratory rather than natural settings. One of these mutations, D151G, appears to arise in the NA of recent human H3N2 viruses upon passage in tissue culture. We inadvertently isolated the second of these mutations, G147R, in the NA of the lab-adapted A/WSN/33 (H1N1) strain while we were passaging a heavily engineered virus in the lab. G147R also occurs at low frequencies in the reported sequences of viruses from three different lineages: human 2009 pandemic H1N1 (pdmH1N1), human seasonal H1N1, and chicken H5N1. Here we reconstructed a representative G147R NA from each of these lineages and found that all of the proteins have acquired the ability to bind an unknown cellular receptor while retaining substantial sialidase activity. We then reconstructed a virus with the HA and NA of a reported G147R pdmH1N1 variant and found no attenuation of viral replication in cell culture or change in pathogenesis in mice. Furthermore, the G147R virus had modestly enhanced resistance to neutralization by the Fab of an antibody against the receptor-binding pocket of HA, although it remained completely sensitive to the full-length IgG. Overall, our results suggest that circulating N1 viruses occasionally may acquire the G147R NA receptor-binding mutation without impairment of replicative capacity.",-1),l=[o,s];function c(u,h,d,p,m,f){return n(),t("div",null,l)}const b=a(r,[["render",c]]);export{v as __pageData,b as default}; diff --git a/assets/papers_2015_machkovech.md.Cs7k8YgY.js b/assets/papers_2015_machkovech.md.Bf5MUNip.js similarity index 97% rename from assets/papers_2015_machkovech.md.Cs7k8YgY.js rename to assets/papers_2015_machkovech.md.Bf5MUNip.js index bb220b4..1c1e0ef 100644 --- a/assets/papers_2015_machkovech.md.Cs7k8YgY.js +++ b/assets/papers_2015_machkovech.md.Bf5MUNip.js @@ -1 +1 @@ -import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages","description":"","frontmatter":{"layout":"paper","title":"Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages","date":"2015-11-15","authors":["Heather M Machkovech","Trevor Bedford","Marc A Suchard","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.01571-15","link":"https://journals.asm.org/doi/full/10.1128/jvi.01571-15","image":"/assets/papers/2015_machkovech.jpg","keywords":["Influenza"]},"headers":[],"relativePath":"papers/2015_machkovech.md","filePath":"papers/2015_machkovech.md"}'),s={name:"papers/2015_machkovech.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Numerous experimental studies have demonstrated that CD8+ T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8+ T cells. Here we use a novel computational approach to test for selection in CD8+ T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8+ T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8+ T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8+ T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint.",-1),l=[o,r];function c(h,u,p,d,m,f){return i(),a("div",null,l)}const _=t(s,[["render",c]]);export{g as __pageData,_ as default}; +import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages","description":"","frontmatter":{"layout":"paper","title":"Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages","date":"2015-11-15","authors":["Heather M Machkovech","Trevor Bedford","Marc A Suchard","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.01571-15","link":"https://journals.asm.org/doi/full/10.1128/jvi.01571-15","image":"/assets/papers/2015_machkovech.jpg","keywords":["Influenza"]},"headers":[],"relativePath":"papers/2015_machkovech.md","filePath":"papers/2015_machkovech.md"}'),s={name:"papers/2015_machkovech.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Numerous experimental studies have demonstrated that CD8+ T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8+ T cells. Here we use a novel computational approach to test for selection in CD8+ T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8+ T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8+ T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8+ T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint.",-1),l=[o,r];function c(h,u,p,d,m,f){return i(),a("div",null,l)}const _=t(s,[["render",c]]);export{g as __pageData,_ as default}; diff --git a/assets/papers_2015_machkovech.md.Cs7k8YgY.lean.js b/assets/papers_2015_machkovech.md.Bf5MUNip.lean.js similarity index 97% rename from assets/papers_2015_machkovech.md.Cs7k8YgY.lean.js rename to assets/papers_2015_machkovech.md.Bf5MUNip.lean.js index bb220b4..1c1e0ef 100644 --- a/assets/papers_2015_machkovech.md.Cs7k8YgY.lean.js +++ b/assets/papers_2015_machkovech.md.Bf5MUNip.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages","description":"","frontmatter":{"layout":"paper","title":"Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages","date":"2015-11-15","authors":["Heather M Machkovech","Trevor Bedford","Marc A Suchard","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.01571-15","link":"https://journals.asm.org/doi/full/10.1128/jvi.01571-15","image":"/assets/papers/2015_machkovech.jpg","keywords":["Influenza"]},"headers":[],"relativePath":"papers/2015_machkovech.md","filePath":"papers/2015_machkovech.md"}'),s={name:"papers/2015_machkovech.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Numerous experimental studies have demonstrated that CD8+ T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8+ T cells. Here we use a novel computational approach to test for selection in CD8+ T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8+ T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8+ T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8+ T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint.",-1),l=[o,r];function c(h,u,p,d,m,f){return i(),a("div",null,l)}const _=t(s,[["render",c]]);export{g as __pageData,_ as default}; +import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages","description":"","frontmatter":{"layout":"paper","title":"Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages","date":"2015-11-15","authors":["Heather M Machkovech","Trevor Bedford","Marc A Suchard","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.01571-15","link":"https://journals.asm.org/doi/full/10.1128/jvi.01571-15","image":"/assets/papers/2015_machkovech.jpg","keywords":["Influenza"]},"headers":[],"relativePath":"papers/2015_machkovech.md","filePath":"papers/2015_machkovech.md"}'),s={name:"papers/2015_machkovech.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Numerous experimental studies have demonstrated that CD8+ T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8+ T cells. Here we use a novel computational approach to test for selection in CD8+ T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8+ T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8+ T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8+ T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint.",-1),l=[o,r];function c(h,u,p,d,m,f){return i(),a("div",null,l)}const _=t(s,[["render",c]]);export{g as __pageData,_ as default}; diff --git a/assets/papers_2016_doud.md.CXy43c_U.js b/assets/papers_2016_doud.md.DkRFPPp6.js similarity index 94% rename from assets/papers_2016_doud.md.CXy43c_U.js rename to assets/papers_2016_doud.md.DkRFPPp6.js index b8ef78c..f18c7c3 100644 --- a/assets/papers_2016_doud.md.CXy43c_U.js +++ b/assets/papers_2016_doud.md.DkRFPPp6.js @@ -1 +1 @@ -import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const v=JSON.parse('{"title":"Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin","date":"2016-06-03","authors":["Michael B Doud","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v8060155","link":"https://www.mdpi.com/1999-4915/8/6/155","image":"/assets/papers/2016_doud.jpg","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2016_doud.md","filePath":"papers/2016_doud.md"}'),i={name:"papers/2016_doud.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza genes evolve mostly via point mutations, and so knowing the effect of every amino-acid mutation provides information about evolutionary paths available to the virus. We and others have combined high-throughput mutagenesis with deep sequencing to estimate the effects of large numbers of mutations to influenza genes. However, these measurements have suffered from substantial experimental noise due to a variety of technical problems, the most prominent of which is bottlenecking during the generation of mutant viruses from plasmids. Here we describe advances that ameliorate these problems, enabling us to measure with greatly improved accuracy and reproducibility the effects of all amino-acid mutations to an H1 influenza hemagglutinin on viral replication in cell culture. The largest improvements come from using a helper virus to reduce bottlenecks when generating viruses from plasmids. Our measurements confirm at much higher resolution the results of previous studies suggesting that antigenic sites on the globular head of hemagglutinin are highly tolerant of mutations. We also show that other regions of hemagglutinin—including the stalk epitopes targeted by broadly neutralizing antibodies—have a much lower inherent capacity to tolerate point mutations. The ability to accurately measure the effects of all influenza mutations should enhance efforts to understand and predict viral evolution.",-1),l=[s,r];function u(c,m,h,d,f,p){return o(),a("div",null,l)}const b=t(i,[["render",u]]);export{v as __pageData,b as default}; +import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const v=JSON.parse('{"title":"Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin","date":"2016-06-03","authors":["Michael B Doud","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v8060155","link":"https://www.mdpi.com/1999-4915/8/6/155","image":"/assets/papers/2016_doud.jpg","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2016_doud.md","filePath":"papers/2016_doud.md"}'),i={name:"papers/2016_doud.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza genes evolve mostly via point mutations, and so knowing the effect of every amino-acid mutation provides information about evolutionary paths available to the virus. We and others have combined high-throughput mutagenesis with deep sequencing to estimate the effects of large numbers of mutations to influenza genes. However, these measurements have suffered from substantial experimental noise due to a variety of technical problems, the most prominent of which is bottlenecking during the generation of mutant viruses from plasmids. Here we describe advances that ameliorate these problems, enabling us to measure with greatly improved accuracy and reproducibility the effects of all amino-acid mutations to an H1 influenza hemagglutinin on viral replication in cell culture. The largest improvements come from using a helper virus to reduce bottlenecks when generating viruses from plasmids. Our measurements confirm at much higher resolution the results of previous studies suggesting that antigenic sites on the globular head of hemagglutinin are highly tolerant of mutations. We also show that other regions of hemagglutinin—including the stalk epitopes targeted by broadly neutralizing antibodies—have a much lower inherent capacity to tolerate point mutations. The ability to accurately measure the effects of all influenza mutations should enhance efforts to understand and predict viral evolution.",-1),l=[s,r];function u(c,m,h,d,f,p){return o(),a("div",null,l)}const b=t(i,[["render",u]]);export{v as __pageData,b as default}; diff --git a/assets/papers_2016_doud.md.CXy43c_U.lean.js b/assets/papers_2016_doud.md.DkRFPPp6.lean.js similarity index 94% rename from assets/papers_2016_doud.md.CXy43c_U.lean.js rename to assets/papers_2016_doud.md.DkRFPPp6.lean.js index b8ef78c..f18c7c3 100644 --- a/assets/papers_2016_doud.md.CXy43c_U.lean.js +++ b/assets/papers_2016_doud.md.DkRFPPp6.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const v=JSON.parse('{"title":"Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin","date":"2016-06-03","authors":["Michael B Doud","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v8060155","link":"https://www.mdpi.com/1999-4915/8/6/155","image":"/assets/papers/2016_doud.jpg","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2016_doud.md","filePath":"papers/2016_doud.md"}'),i={name:"papers/2016_doud.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza genes evolve mostly via point mutations, and so knowing the effect of every amino-acid mutation provides information about evolutionary paths available to the virus. We and others have combined high-throughput mutagenesis with deep sequencing to estimate the effects of large numbers of mutations to influenza genes. However, these measurements have suffered from substantial experimental noise due to a variety of technical problems, the most prominent of which is bottlenecking during the generation of mutant viruses from plasmids. Here we describe advances that ameliorate these problems, enabling us to measure with greatly improved accuracy and reproducibility the effects of all amino-acid mutations to an H1 influenza hemagglutinin on viral replication in cell culture. The largest improvements come from using a helper virus to reduce bottlenecks when generating viruses from plasmids. Our measurements confirm at much higher resolution the results of previous studies suggesting that antigenic sites on the globular head of hemagglutinin are highly tolerant of mutations. We also show that other regions of hemagglutinin—including the stalk epitopes targeted by broadly neutralizing antibodies—have a much lower inherent capacity to tolerate point mutations. The ability to accurately measure the effects of all influenza mutations should enhance efforts to understand and predict viral evolution.",-1),l=[s,r];function u(c,m,h,d,f,p){return o(),a("div",null,l)}const b=t(i,[["render",u]]);export{v as __pageData,b as default}; +import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const v=JSON.parse('{"title":"Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin","date":"2016-06-03","authors":["Michael B Doud","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v8060155","link":"https://www.mdpi.com/1999-4915/8/6/155","image":"/assets/papers/2016_doud.jpg","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2016_doud.md","filePath":"papers/2016_doud.md"}'),i={name:"papers/2016_doud.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza genes evolve mostly via point mutations, and so knowing the effect of every amino-acid mutation provides information about evolutionary paths available to the virus. We and others have combined high-throughput mutagenesis with deep sequencing to estimate the effects of large numbers of mutations to influenza genes. However, these measurements have suffered from substantial experimental noise due to a variety of technical problems, the most prominent of which is bottlenecking during the generation of mutant viruses from plasmids. Here we describe advances that ameliorate these problems, enabling us to measure with greatly improved accuracy and reproducibility the effects of all amino-acid mutations to an H1 influenza hemagglutinin on viral replication in cell culture. The largest improvements come from using a helper virus to reduce bottlenecks when generating viruses from plasmids. Our measurements confirm at much higher resolution the results of previous studies suggesting that antigenic sites on the globular head of hemagglutinin are highly tolerant of mutations. We also show that other regions of hemagglutinin—including the stalk epitopes targeted by broadly neutralizing antibodies—have a much lower inherent capacity to tolerate point mutations. The ability to accurately measure the effects of all influenza mutations should enhance efforts to understand and predict viral evolution.",-1),l=[s,r];function u(c,m,h,d,f,p){return o(),a("div",null,l)}const b=t(i,[["render",u]]);export{v as __pageData,b as default}; diff --git a/assets/papers_2016_haddox.md.I0WzcTfP.js b/assets/papers_2016_haddox.md.nBWTXwbj.js similarity index 97% rename from assets/papers_2016_haddox.md.I0WzcTfP.js rename to assets/papers_2016_haddox.md.nBWTXwbj.js index 5addae0..3762da4 100644 --- a/assets/papers_2016_haddox.md.I0WzcTfP.js +++ b/assets/papers_2016_haddox.md.nBWTXwbj.js @@ -1 +1 @@ -import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const v=JSON.parse('{"title":"Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture","description":"","frontmatter":{"layout":"paper","title":"Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture","date":"2016-12-13","authors":["Hugh K Haddox","Adam S Dingens","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1006114","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006114","image":"/assets/papers/2016_haddox.png","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2016_haddox.md","filePath":"papers/2016_haddox.md"}'),i={name:"papers/2016_haddox.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"HIV is notorious for its capacity to evade immunity and anti-viral drugs through rapid sequence evolution. Knowledge of the functional effects of mutations to HIV is critical for understanding this evolution. HIV’s most rapidly evolving protein is its envelope (Env). Here we use deep mutational scanning to experimentally estimate the effects of all amino-acid mutations to Env on viral replication in cell culture. Most mutations are under purifying selection in our experiments, although a few sites experience strong selection for mutations that enhance HIV’s replication in cell culture. We compare our experimental measurements of each site’s preference for each amino acid to the actual frequencies of these amino acids in naturally occurring HIV sequences. Our measured amino-acid preferences correlate with amino-acid frequencies in natural sequences for most sites. However, our measured preferences are less concordant with natural amino-acid frequencies at surface-exposed sites that are subject to pressures absent from our experiments such as antibody selection. Our data enable us to quantify the inherent mutational tolerance of each site in Env. We show that the epitopes of broadly neutralizing antibodies have a significantly reduced inherent capacity to tolerate mutations, rigorously validating a pervasive idea in the field. Overall, our results help disentangle the role of inherent functional constraints and external selection pressures in shaping Env’s evolution.",-1),l=[s,r];function c(u,d,p,h,m,f){return n(),a("div",null,l)}const _=t(i,[["render",c]]);export{v as __pageData,_ as default}; +import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const v=JSON.parse('{"title":"Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture","description":"","frontmatter":{"layout":"paper","title":"Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture","date":"2016-12-13","authors":["Hugh K Haddox","Adam S Dingens","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1006114","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006114","image":"/assets/papers/2016_haddox.png","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2016_haddox.md","filePath":"papers/2016_haddox.md"}'),i={name:"papers/2016_haddox.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"HIV is notorious for its capacity to evade immunity and anti-viral drugs through rapid sequence evolution. Knowledge of the functional effects of mutations to HIV is critical for understanding this evolution. HIV’s most rapidly evolving protein is its envelope (Env). Here we use deep mutational scanning to experimentally estimate the effects of all amino-acid mutations to Env on viral replication in cell culture. Most mutations are under purifying selection in our experiments, although a few sites experience strong selection for mutations that enhance HIV’s replication in cell culture. We compare our experimental measurements of each site’s preference for each amino acid to the actual frequencies of these amino acids in naturally occurring HIV sequences. Our measured amino-acid preferences correlate with amino-acid frequencies in natural sequences for most sites. However, our measured preferences are less concordant with natural amino-acid frequencies at surface-exposed sites that are subject to pressures absent from our experiments such as antibody selection. Our data enable us to quantify the inherent mutational tolerance of each site in Env. We show that the epitopes of broadly neutralizing antibodies have a significantly reduced inherent capacity to tolerate mutations, rigorously validating a pervasive idea in the field. Overall, our results help disentangle the role of inherent functional constraints and external selection pressures in shaping Env’s evolution.",-1),l=[s,r];function c(u,d,p,h,m,f){return n(),a("div",null,l)}const _=t(i,[["render",c]]);export{v as __pageData,_ as default}; diff --git a/assets/papers_2016_haddox.md.I0WzcTfP.lean.js b/assets/papers_2016_haddox.md.nBWTXwbj.lean.js similarity index 97% rename from assets/papers_2016_haddox.md.I0WzcTfP.lean.js rename to assets/papers_2016_haddox.md.nBWTXwbj.lean.js index 5addae0..3762da4 100644 --- a/assets/papers_2016_haddox.md.I0WzcTfP.lean.js +++ b/assets/papers_2016_haddox.md.nBWTXwbj.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const v=JSON.parse('{"title":"Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture","description":"","frontmatter":{"layout":"paper","title":"Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture","date":"2016-12-13","authors":["Hugh K Haddox","Adam S Dingens","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1006114","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006114","image":"/assets/papers/2016_haddox.png","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2016_haddox.md","filePath":"papers/2016_haddox.md"}'),i={name:"papers/2016_haddox.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"HIV is notorious for its capacity to evade immunity and anti-viral drugs through rapid sequence evolution. Knowledge of the functional effects of mutations to HIV is critical for understanding this evolution. HIV’s most rapidly evolving protein is its envelope (Env). Here we use deep mutational scanning to experimentally estimate the effects of all amino-acid mutations to Env on viral replication in cell culture. Most mutations are under purifying selection in our experiments, although a few sites experience strong selection for mutations that enhance HIV’s replication in cell culture. We compare our experimental measurements of each site’s preference for each amino acid to the actual frequencies of these amino acids in naturally occurring HIV sequences. Our measured amino-acid preferences correlate with amino-acid frequencies in natural sequences for most sites. However, our measured preferences are less concordant with natural amino-acid frequencies at surface-exposed sites that are subject to pressures absent from our experiments such as antibody selection. Our data enable us to quantify the inherent mutational tolerance of each site in Env. We show that the epitopes of broadly neutralizing antibodies have a significantly reduced inherent capacity to tolerate mutations, rigorously validating a pervasive idea in the field. Overall, our results help disentangle the role of inherent functional constraints and external selection pressures in shaping Env’s evolution.",-1),l=[s,r];function c(u,d,p,h,m,f){return n(),a("div",null,l)}const _=t(i,[["render",c]]);export{v as __pageData,_ as default}; +import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const v=JSON.parse('{"title":"Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture","description":"","frontmatter":{"layout":"paper","title":"Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture","date":"2016-12-13","authors":["Hugh K Haddox","Adam S Dingens","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1006114","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006114","image":"/assets/papers/2016_haddox.png","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2016_haddox.md","filePath":"papers/2016_haddox.md"}'),i={name:"papers/2016_haddox.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"HIV is notorious for its capacity to evade immunity and anti-viral drugs through rapid sequence evolution. Knowledge of the functional effects of mutations to HIV is critical for understanding this evolution. HIV’s most rapidly evolving protein is its envelope (Env). Here we use deep mutational scanning to experimentally estimate the effects of all amino-acid mutations to Env on viral replication in cell culture. Most mutations are under purifying selection in our experiments, although a few sites experience strong selection for mutations that enhance HIV’s replication in cell culture. We compare our experimental measurements of each site’s preference for each amino acid to the actual frequencies of these amino acids in naturally occurring HIV sequences. Our measured amino-acid preferences correlate with amino-acid frequencies in natural sequences for most sites. However, our measured preferences are less concordant with natural amino-acid frequencies at surface-exposed sites that are subject to pressures absent from our experiments such as antibody selection. Our data enable us to quantify the inherent mutational tolerance of each site in Env. We show that the epitopes of broadly neutralizing antibodies have a significantly reduced inherent capacity to tolerate mutations, rigorously validating a pervasive idea in the field. Overall, our results help disentangle the role of inherent functional constraints and external selection pressures in shaping Env’s evolution.",-1),l=[s,r];function c(u,d,p,h,m,f){return n(),a("div",null,l)}const _=t(i,[["render",c]]);export{v as __pageData,_ as default}; diff --git a/assets/papers_2016_xue.md.Bh1SkzbY.js b/assets/papers_2016_xue.md.8q0P6h_J.js similarity index 96% rename from assets/papers_2016_xue.md.Bh1SkzbY.js rename to assets/papers_2016_xue.md.8q0P6h_J.js index 5720f94..51b8fba 100644 --- a/assets/papers_2016_xue.md.Bh1SkzbY.js +++ b/assets/papers_2016_xue.md.8q0P6h_J.js @@ -1 +1 @@ -import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture","description":"","frontmatter":{"layout":"paper","title":"Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture","date":"2016-03-15","authors":["Katherine S Xue","Kathryn A Hooper","Anja R Ollodart","Adam S Dingens","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.13974.001","link":"https://elifesciences.org/articles/13974","image":"/assets/papers/2016_xue.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2016_xue.md","filePath":"papers/2016_xue.md"}'),o={name:"papers/2016_xue.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"RNA viruses rapidly diversify into quasispecies of related genotypes. This genetic diversity has long been known to facilitate adaptation, but recent studies have suggested that cooperation between variants might also increase population fitness. Here, we demonstrate strong cooperation between two H3N2 influenza variants that differ by a single mutation at residue 151 in neuraminidase, which normally mediates viral exit from host cells. Residue 151 is often annotated as an ambiguous amino acid in sequenced isolates, indicating mixed viral populations. We show that mixed populations grow better than either variant alone in cell culture. Pure populations of either variant generate the other through mutation and then stably maintain a mix of the two genotypes. We suggest that cooperation arises because mixed populations combine one variant’s proficiency at cell entry with the other’s proficiency at cell exit. Our work demonstrates a specific cooperative interaction between defined variants in a viral quasispecies.",-1),l=[s,r];function c(p,d,u,h,f,m){return i(),a("div",null,l)}const v=t(o,[["render",c]]);export{_ as __pageData,v as default}; +import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture","description":"","frontmatter":{"layout":"paper","title":"Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture","date":"2016-03-15","authors":["Katherine S Xue","Kathryn A Hooper","Anja R Ollodart","Adam S Dingens","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.13974.001","link":"https://elifesciences.org/articles/13974","image":"/assets/papers/2016_xue.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2016_xue.md","filePath":"papers/2016_xue.md"}'),o={name:"papers/2016_xue.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"RNA viruses rapidly diversify into quasispecies of related genotypes. This genetic diversity has long been known to facilitate adaptation, but recent studies have suggested that cooperation between variants might also increase population fitness. Here, we demonstrate strong cooperation between two H3N2 influenza variants that differ by a single mutation at residue 151 in neuraminidase, which normally mediates viral exit from host cells. Residue 151 is often annotated as an ambiguous amino acid in sequenced isolates, indicating mixed viral populations. We show that mixed populations grow better than either variant alone in cell culture. Pure populations of either variant generate the other through mutation and then stably maintain a mix of the two genotypes. We suggest that cooperation arises because mixed populations combine one variant’s proficiency at cell entry with the other’s proficiency at cell exit. Our work demonstrates a specific cooperative interaction between defined variants in a viral quasispecies.",-1),l=[s,r];function c(p,d,u,h,f,m){return i(),a("div",null,l)}const v=t(o,[["render",c]]);export{_ as __pageData,v as default}; diff --git a/assets/papers_2016_xue.md.Bh1SkzbY.lean.js b/assets/papers_2016_xue.md.8q0P6h_J.lean.js similarity index 96% rename from assets/papers_2016_xue.md.Bh1SkzbY.lean.js rename to assets/papers_2016_xue.md.8q0P6h_J.lean.js index 5720f94..51b8fba 100644 --- a/assets/papers_2016_xue.md.Bh1SkzbY.lean.js +++ b/assets/papers_2016_xue.md.8q0P6h_J.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture","description":"","frontmatter":{"layout":"paper","title":"Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture","date":"2016-03-15","authors":["Katherine S Xue","Kathryn A Hooper","Anja R Ollodart","Adam S Dingens","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.13974.001","link":"https://elifesciences.org/articles/13974","image":"/assets/papers/2016_xue.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2016_xue.md","filePath":"papers/2016_xue.md"}'),o={name:"papers/2016_xue.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"RNA viruses rapidly diversify into quasispecies of related genotypes. This genetic diversity has long been known to facilitate adaptation, but recent studies have suggested that cooperation between variants might also increase population fitness. Here, we demonstrate strong cooperation between two H3N2 influenza variants that differ by a single mutation at residue 151 in neuraminidase, which normally mediates viral exit from host cells. Residue 151 is often annotated as an ambiguous amino acid in sequenced isolates, indicating mixed viral populations. We show that mixed populations grow better than either variant alone in cell culture. Pure populations of either variant generate the other through mutation and then stably maintain a mix of the two genotypes. We suggest that cooperation arises because mixed populations combine one variant’s proficiency at cell entry with the other’s proficiency at cell exit. Our work demonstrates a specific cooperative interaction between defined variants in a viral quasispecies.",-1),l=[s,r];function c(p,d,u,h,f,m){return i(),a("div",null,l)}const v=t(o,[["render",c]]);export{_ as __pageData,v as default}; +import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture","description":"","frontmatter":{"layout":"paper","title":"Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture","date":"2016-03-15","authors":["Katherine S Xue","Kathryn A Hooper","Anja R Ollodart","Adam S Dingens","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.13974.001","link":"https://elifesciences.org/articles/13974","image":"/assets/papers/2016_xue.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2016_xue.md","filePath":"papers/2016_xue.md"}'),o={name:"papers/2016_xue.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"RNA viruses rapidly diversify into quasispecies of related genotypes. This genetic diversity has long been known to facilitate adaptation, but recent studies have suggested that cooperation between variants might also increase population fitness. Here, we demonstrate strong cooperation between two H3N2 influenza variants that differ by a single mutation at residue 151 in neuraminidase, which normally mediates viral exit from host cells. Residue 151 is often annotated as an ambiguous amino acid in sequenced isolates, indicating mixed viral populations. We show that mixed populations grow better than either variant alone in cell culture. Pure populations of either variant generate the other through mutation and then stably maintain a mix of the two genotypes. We suggest that cooperation arises because mixed populations combine one variant’s proficiency at cell entry with the other’s proficiency at cell exit. Our work demonstrates a specific cooperative interaction between defined variants in a viral quasispecies.",-1),l=[s,r];function c(p,d,u,h,f,m){return i(),a("div",null,l)}const v=t(o,[["render",c]]);export{_ as __pageData,v as default}; diff --git a/assets/papers_2017_ashenberg.md.Ci2ysF7X.js b/assets/papers_2017_ashenberg.md.Df9IJNfu.js similarity index 97% rename from assets/papers_2017_ashenberg.md.Ci2ysF7X.js rename to assets/papers_2017_ashenberg.md.Df9IJNfu.js index 55615f1..9eba6e0 100644 --- a/assets/papers_2017_ashenberg.md.Ci2ysF7X.js +++ b/assets/papers_2017_ashenberg.md.Df9IJNfu.js @@ -1 +1 @@ -import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA","date":"2017-03-27","authors":["Orr Ashenberg","Jai Padmakumar","Michael B Doud","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1006288","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006288","image":"/assets/papers/2017_ashenberg.png","keywords":["Deep mutational scanning","Influenza"]},"headers":[],"relativePath":"papers/2017_ashenberg.md","filePath":"papers/2017_ashenberg.md"}'),s={name:"papers/2017_ashenberg.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The innate-immune restriction factor MxA inhibits influenza replication by targeting the viral nucleoprotein (NP). Human influenza virus is more resistant than avian influenza virus to inhibition by human MxA, and prior work has compared human and avian viral strains to identify amino-acid differences in NP that affect sensitivity to MxA. However, this strategy is limited to identifying sites in NP where mutations that affect MxA sensitivity have fixed during the small number of documented zoonotic transmissions of influenza to humans. Here we use an unbiased deep mutational scanning approach to quantify how all single amino-acid mutations to NP affect MxA sensitivity in the context of replication-competent virus. We both identify new sites in NP where mutations affect MxA resistance and re-identify mutations known to have increased MxA resistance during historical adaptations of influenza to humans. Most of the sites where mutations have the greatest effect are almost completely conserved across all influenza A viruses, and the amino acids at these sites confer relatively high resistance to MxA. These sites cluster in regions of NP that appear to be important for its recognition by MxA. Overall, our work systematically identifies the sites in influenza nucleoprotein where mutations affect sensitivity to MxA. We also demonstrate a powerful new strategy for identifying regions of viral proteins that affect inhibition by host factors.",-1),l=[o,r];function c(h,f,u,d,p,m){return i(),a("div",null,l)}const v=t(s,[["render",c]]);export{b as __pageData,v as default}; +import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA","date":"2017-03-27","authors":["Orr Ashenberg","Jai Padmakumar","Michael B Doud","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1006288","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006288","image":"/assets/papers/2017_ashenberg.png","keywords":["Deep mutational scanning","Influenza"]},"headers":[],"relativePath":"papers/2017_ashenberg.md","filePath":"papers/2017_ashenberg.md"}'),s={name:"papers/2017_ashenberg.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The innate-immune restriction factor MxA inhibits influenza replication by targeting the viral nucleoprotein (NP). Human influenza virus is more resistant than avian influenza virus to inhibition by human MxA, and prior work has compared human and avian viral strains to identify amino-acid differences in NP that affect sensitivity to MxA. However, this strategy is limited to identifying sites in NP where mutations that affect MxA sensitivity have fixed during the small number of documented zoonotic transmissions of influenza to humans. Here we use an unbiased deep mutational scanning approach to quantify how all single amino-acid mutations to NP affect MxA sensitivity in the context of replication-competent virus. We both identify new sites in NP where mutations affect MxA resistance and re-identify mutations known to have increased MxA resistance during historical adaptations of influenza to humans. Most of the sites where mutations have the greatest effect are almost completely conserved across all influenza A viruses, and the amino acids at these sites confer relatively high resistance to MxA. These sites cluster in regions of NP that appear to be important for its recognition by MxA. Overall, our work systematically identifies the sites in influenza nucleoprotein where mutations affect sensitivity to MxA. We also demonstrate a powerful new strategy for identifying regions of viral proteins that affect inhibition by host factors.",-1),l=[o,r];function c(h,f,u,d,p,m){return i(),a("div",null,l)}const v=t(s,[["render",c]]);export{b as __pageData,v as default}; diff --git a/assets/papers_2017_ashenberg.md.Ci2ysF7X.lean.js b/assets/papers_2017_ashenberg.md.Df9IJNfu.lean.js similarity index 97% rename from assets/papers_2017_ashenberg.md.Ci2ysF7X.lean.js rename to assets/papers_2017_ashenberg.md.Df9IJNfu.lean.js index 55615f1..9eba6e0 100644 --- a/assets/papers_2017_ashenberg.md.Ci2ysF7X.lean.js +++ b/assets/papers_2017_ashenberg.md.Df9IJNfu.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA","date":"2017-03-27","authors":["Orr Ashenberg","Jai Padmakumar","Michael B Doud","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1006288","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006288","image":"/assets/papers/2017_ashenberg.png","keywords":["Deep mutational scanning","Influenza"]},"headers":[],"relativePath":"papers/2017_ashenberg.md","filePath":"papers/2017_ashenberg.md"}'),s={name:"papers/2017_ashenberg.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The innate-immune restriction factor MxA inhibits influenza replication by targeting the viral nucleoprotein (NP). Human influenza virus is more resistant than avian influenza virus to inhibition by human MxA, and prior work has compared human and avian viral strains to identify amino-acid differences in NP that affect sensitivity to MxA. However, this strategy is limited to identifying sites in NP where mutations that affect MxA sensitivity have fixed during the small number of documented zoonotic transmissions of influenza to humans. Here we use an unbiased deep mutational scanning approach to quantify how all single amino-acid mutations to NP affect MxA sensitivity in the context of replication-competent virus. We both identify new sites in NP where mutations affect MxA resistance and re-identify mutations known to have increased MxA resistance during historical adaptations of influenza to humans. Most of the sites where mutations have the greatest effect are almost completely conserved across all influenza A viruses, and the amino acids at these sites confer relatively high resistance to MxA. These sites cluster in regions of NP that appear to be important for its recognition by MxA. Overall, our work systematically identifies the sites in influenza nucleoprotein where mutations affect sensitivity to MxA. We also demonstrate a powerful new strategy for identifying regions of viral proteins that affect inhibition by host factors.",-1),l=[o,r];function c(h,f,u,d,p,m){return i(),a("div",null,l)}const v=t(s,[["render",c]]);export{b as __pageData,v as default}; +import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA","date":"2017-03-27","authors":["Orr Ashenberg","Jai Padmakumar","Michael B Doud","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1006288","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006288","image":"/assets/papers/2017_ashenberg.png","keywords":["Deep mutational scanning","Influenza"]},"headers":[],"relativePath":"papers/2017_ashenberg.md","filePath":"papers/2017_ashenberg.md"}'),s={name:"papers/2017_ashenberg.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The innate-immune restriction factor MxA inhibits influenza replication by targeting the viral nucleoprotein (NP). Human influenza virus is more resistant than avian influenza virus to inhibition by human MxA, and prior work has compared human and avian viral strains to identify amino-acid differences in NP that affect sensitivity to MxA. However, this strategy is limited to identifying sites in NP where mutations that affect MxA sensitivity have fixed during the small number of documented zoonotic transmissions of influenza to humans. Here we use an unbiased deep mutational scanning approach to quantify how all single amino-acid mutations to NP affect MxA sensitivity in the context of replication-competent virus. We both identify new sites in NP where mutations affect MxA resistance and re-identify mutations known to have increased MxA resistance during historical adaptations of influenza to humans. Most of the sites where mutations have the greatest effect are almost completely conserved across all influenza A viruses, and the amino acids at these sites confer relatively high resistance to MxA. These sites cluster in regions of NP that appear to be important for its recognition by MxA. Overall, our work systematically identifies the sites in influenza nucleoprotein where mutations affect sensitivity to MxA. We also demonstrate a powerful new strategy for identifying regions of viral proteins that affect inhibition by host factors.",-1),l=[o,r];function c(h,f,u,d,p,m){return i(),a("div",null,l)}const v=t(s,[["render",c]]);export{b as __pageData,v as default}; diff --git a/assets/papers_2017_bloom.md.BAGuDh3D.js b/assets/papers_2017_bloom.md.CGsqWTko.js similarity index 95% rename from assets/papers_2017_bloom.md.BAGuDh3D.js rename to assets/papers_2017_bloom.md.CGsqWTko.js index 4cbe5cf..39ffe13 100644 --- a/assets/papers_2017_bloom.md.BAGuDh3D.js +++ b/assets/papers_2017_bloom.md.CGsqWTko.js @@ -1 +1 @@ -import{_ as t,c as o,o as s,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models","description":"","frontmatter":{"layout":"paper","title":"Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models","date":"2017-12-01","authors":["Jesse D Bloom"],"journal":"Biology direct","doi":"10.1186/s13062-016-0172-z","link":"https://link.springer.com/article/10.1186/s13062-016-0172-z","image":"/assets/papers/2017_bloom.jpg","keywords":["Phylogenetics"]},"headers":[],"relativePath":"papers/2017_bloom.md","filePath":"papers/2017_bloom.md"}'),a={name:"papers/2017_bloom.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Sites of positive selection are identified by comparing observed evolutionary patterns to those expected under a null model for evolution in the absence of such selection. For protein-coding genes, the most common null model is that nonsynonymous and synonymous mutations fix at equal rates; this unrealistic model has limited power to detect many interesting forms of selection.",-1),l=[n,r];function c(d,m,p,f,_,u){return s(),o("div",null,l)}const y=t(a,[["render",c]]);export{b as __pageData,y as default}; +import{_ as t,c as o,o as s,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models","description":"","frontmatter":{"layout":"paper","title":"Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models","date":"2017-12-01","authors":["Jesse D Bloom"],"journal":"Biology direct","doi":"10.1186/s13062-016-0172-z","link":"https://link.springer.com/article/10.1186/s13062-016-0172-z","image":"/assets/papers/2017_bloom.jpg","keywords":["Phylogenetics"]},"headers":[],"relativePath":"papers/2017_bloom.md","filePath":"papers/2017_bloom.md"}'),a={name:"papers/2017_bloom.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Sites of positive selection are identified by comparing observed evolutionary patterns to those expected under a null model for evolution in the absence of such selection. For protein-coding genes, the most common null model is that nonsynonymous and synonymous mutations fix at equal rates; this unrealistic model has limited power to detect many interesting forms of selection.",-1),l=[n,r];function c(d,m,p,f,_,u){return s(),o("div",null,l)}const y=t(a,[["render",c]]);export{b as __pageData,y as default}; diff --git a/assets/papers_2017_bloom.md.BAGuDh3D.lean.js b/assets/papers_2017_bloom.md.CGsqWTko.lean.js similarity index 95% rename from assets/papers_2017_bloom.md.BAGuDh3D.lean.js rename to assets/papers_2017_bloom.md.CGsqWTko.lean.js index 4cbe5cf..39ffe13 100644 --- a/assets/papers_2017_bloom.md.BAGuDh3D.lean.js +++ b/assets/papers_2017_bloom.md.CGsqWTko.lean.js @@ -1 +1 @@ -import{_ as t,c as o,o as s,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models","description":"","frontmatter":{"layout":"paper","title":"Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models","date":"2017-12-01","authors":["Jesse D Bloom"],"journal":"Biology direct","doi":"10.1186/s13062-016-0172-z","link":"https://link.springer.com/article/10.1186/s13062-016-0172-z","image":"/assets/papers/2017_bloom.jpg","keywords":["Phylogenetics"]},"headers":[],"relativePath":"papers/2017_bloom.md","filePath":"papers/2017_bloom.md"}'),a={name:"papers/2017_bloom.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Sites of positive selection are identified by comparing observed evolutionary patterns to those expected under a null model for evolution in the absence of such selection. For protein-coding genes, the most common null model is that nonsynonymous and synonymous mutations fix at equal rates; this unrealistic model has limited power to detect many interesting forms of selection.",-1),l=[n,r];function c(d,m,p,f,_,u){return s(),o("div",null,l)}const y=t(a,[["render",c]]);export{b as __pageData,y as default}; +import{_ as t,c as o,o as s,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models","description":"","frontmatter":{"layout":"paper","title":"Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models","date":"2017-12-01","authors":["Jesse D Bloom"],"journal":"Biology direct","doi":"10.1186/s13062-016-0172-z","link":"https://link.springer.com/article/10.1186/s13062-016-0172-z","image":"/assets/papers/2017_bloom.jpg","keywords":["Phylogenetics"]},"headers":[],"relativePath":"papers/2017_bloom.md","filePath":"papers/2017_bloom.md"}'),a={name:"papers/2017_bloom.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Sites of positive selection are identified by comparing observed evolutionary patterns to those expected under a null model for evolution in the absence of such selection. For protein-coding genes, the most common null model is that nonsynonymous and synonymous mutations fix at equal rates; this unrealistic model has limited power to detect many interesting forms of selection.",-1),l=[n,r];function c(d,m,p,f,_,u){return s(),o("div",null,l)}const y=t(a,[["render",c]]);export{b as __pageData,y as default}; diff --git a/assets/papers_2017_dingens.md.BF18q8bh.js b/assets/papers_2017_dingens.md.Cbmr6FGX.js similarity index 97% rename from assets/papers_2017_dingens.md.BF18q8bh.js rename to assets/papers_2017_dingens.md.Cbmr6FGX.js index 667e1dc..0055019 100644 --- a/assets/papers_2017_dingens.md.BF18q8bh.js +++ b/assets/papers_2017_dingens.md.Cbmr6FGX.js @@ -1 +1 @@ -import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const v=JSON.parse('{"title":"Comprehensive mapping of HIV-1 escape from a broadly neutralizing antibody","description":"","frontmatter":{"layout":"paper","title":"Comprehensive mapping of HIV-1 escape from a broadly neutralizing antibody","date":"2017-06-14","authors":["Adam S Dingens","Hugh K Haddox","Julie Overbaugh","Jesse D Bloom"],"journal":"Cell host & microbe","doi":"10.1016/j.chom.2017.05.003","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(17)30196-8.pdf","image":"/assets/papers/2017_dingens.jpg","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2017_dingens.md","filePath":"papers/2017_dingens.md"}'),o={name:"papers/2017_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Precisely defining how viral mutations affect HIV’s sensitivity to antibodies is vital to develop and evaluate vaccines and antibody immunotherapeutics. Despite great effort, a full map of escape mutants has not been delineated for an anti-HIV antibody. We describe a massively parallel experimental approach to quantify how all single amino acid mutations to HIV Envelope (Env) affect neutralizing antibody sensitivity in the context of replication-competent virus. We apply this approach to PGT151, a broadly neutralizing antibody recognizing a combination of Env residues and glycans. We confirm sites previously defined by structural and functional studies and reveal additional sites of escape, such as positively charged mutations in the antibody-Env interface. Evaluating the effect of each amino acid at each site lends insight into biochemical mechanisms of escape throughout the epitope, highlighting roles for charge-charge repulsions. Thus, comprehensively mapping HIV antibody escape gives a quantitative, mutation-level view of Env evasion of neutralization.",-1),c=[s,r];function l(d,p,h,m,u,f){return i(),t("div",null,c)}const b=a(o,[["render",l]]);export{v as __pageData,b as default}; +import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const v=JSON.parse('{"title":"Comprehensive mapping of HIV-1 escape from a broadly neutralizing antibody","description":"","frontmatter":{"layout":"paper","title":"Comprehensive mapping of HIV-1 escape from a broadly neutralizing antibody","date":"2017-06-14","authors":["Adam S Dingens","Hugh K Haddox","Julie Overbaugh","Jesse D Bloom"],"journal":"Cell host & microbe","doi":"10.1016/j.chom.2017.05.003","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(17)30196-8.pdf","image":"/assets/papers/2017_dingens.jpg","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2017_dingens.md","filePath":"papers/2017_dingens.md"}'),o={name:"papers/2017_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Precisely defining how viral mutations affect HIV’s sensitivity to antibodies is vital to develop and evaluate vaccines and antibody immunotherapeutics. Despite great effort, a full map of escape mutants has not been delineated for an anti-HIV antibody. We describe a massively parallel experimental approach to quantify how all single amino acid mutations to HIV Envelope (Env) affect neutralizing antibody sensitivity in the context of replication-competent virus. We apply this approach to PGT151, a broadly neutralizing antibody recognizing a combination of Env residues and glycans. We confirm sites previously defined by structural and functional studies and reveal additional sites of escape, such as positively charged mutations in the antibody-Env interface. Evaluating the effect of each amino acid at each site lends insight into biochemical mechanisms of escape throughout the epitope, highlighting roles for charge-charge repulsions. Thus, comprehensively mapping HIV antibody escape gives a quantitative, mutation-level view of Env evasion of neutralization.",-1),c=[s,r];function l(d,p,h,m,u,f){return i(),t("div",null,c)}const b=a(o,[["render",l]]);export{v as __pageData,b as default}; diff --git a/assets/papers_2017_dingens.md.BF18q8bh.lean.js b/assets/papers_2017_dingens.md.Cbmr6FGX.lean.js similarity index 97% rename from assets/papers_2017_dingens.md.BF18q8bh.lean.js rename to assets/papers_2017_dingens.md.Cbmr6FGX.lean.js index 667e1dc..0055019 100644 --- a/assets/papers_2017_dingens.md.BF18q8bh.lean.js +++ b/assets/papers_2017_dingens.md.Cbmr6FGX.lean.js @@ -1 +1 @@ -import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const v=JSON.parse('{"title":"Comprehensive mapping of HIV-1 escape from a broadly neutralizing antibody","description":"","frontmatter":{"layout":"paper","title":"Comprehensive mapping of HIV-1 escape from a broadly neutralizing antibody","date":"2017-06-14","authors":["Adam S Dingens","Hugh K Haddox","Julie Overbaugh","Jesse D Bloom"],"journal":"Cell host & microbe","doi":"10.1016/j.chom.2017.05.003","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(17)30196-8.pdf","image":"/assets/papers/2017_dingens.jpg","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2017_dingens.md","filePath":"papers/2017_dingens.md"}'),o={name:"papers/2017_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Precisely defining how viral mutations affect HIV’s sensitivity to antibodies is vital to develop and evaluate vaccines and antibody immunotherapeutics. Despite great effort, a full map of escape mutants has not been delineated for an anti-HIV antibody. We describe a massively parallel experimental approach to quantify how all single amino acid mutations to HIV Envelope (Env) affect neutralizing antibody sensitivity in the context of replication-competent virus. We apply this approach to PGT151, a broadly neutralizing antibody recognizing a combination of Env residues and glycans. We confirm sites previously defined by structural and functional studies and reveal additional sites of escape, such as positively charged mutations in the antibody-Env interface. Evaluating the effect of each amino acid at each site lends insight into biochemical mechanisms of escape throughout the epitope, highlighting roles for charge-charge repulsions. Thus, comprehensively mapping HIV antibody escape gives a quantitative, mutation-level view of Env evasion of neutralization.",-1),c=[s,r];function l(d,p,h,m,u,f){return i(),t("div",null,c)}const b=a(o,[["render",l]]);export{v as __pageData,b as default}; +import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const v=JSON.parse('{"title":"Comprehensive mapping of HIV-1 escape from a broadly neutralizing antibody","description":"","frontmatter":{"layout":"paper","title":"Comprehensive mapping of HIV-1 escape from a broadly neutralizing antibody","date":"2017-06-14","authors":["Adam S Dingens","Hugh K Haddox","Julie Overbaugh","Jesse D Bloom"],"journal":"Cell host & microbe","doi":"10.1016/j.chom.2017.05.003","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(17)30196-8.pdf","image":"/assets/papers/2017_dingens.jpg","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2017_dingens.md","filePath":"papers/2017_dingens.md"}'),o={name:"papers/2017_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Precisely defining how viral mutations affect HIV’s sensitivity to antibodies is vital to develop and evaluate vaccines and antibody immunotherapeutics. Despite great effort, a full map of escape mutants has not been delineated for an anti-HIV antibody. We describe a massively parallel experimental approach to quantify how all single amino acid mutations to HIV Envelope (Env) affect neutralizing antibody sensitivity in the context of replication-competent virus. We apply this approach to PGT151, a broadly neutralizing antibody recognizing a combination of Env residues and glycans. We confirm sites previously defined by structural and functional studies and reveal additional sites of escape, such as positively charged mutations in the antibody-Env interface. Evaluating the effect of each amino acid at each site lends insight into biochemical mechanisms of escape throughout the epitope, highlighting roles for charge-charge repulsions. Thus, comprehensively mapping HIV antibody escape gives a quantitative, mutation-level view of Env evasion of neutralization.",-1),c=[s,r];function l(d,p,h,m,u,f){return i(),t("div",null,c)}const b=a(o,[["render",l]]);export{v as __pageData,b as default}; diff --git a/assets/papers_2017_doud.md.AtVhWQrn.js b/assets/papers_2017_doud.md.CIblnIx8.js similarity index 97% rename from assets/papers_2017_doud.md.AtVhWQrn.js rename to assets/papers_2017_doud.md.CIblnIx8.js index bd798b6..be7bc90 100644 --- a/assets/papers_2017_doud.md.AtVhWQrn.js +++ b/assets/papers_2017_doud.md.CIblnIx8.js @@ -1 +1 @@ -import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Complete mapping of viral escape from neutralizing antibodies","description":"","frontmatter":{"layout":"paper","title":"Complete mapping of viral escape from neutralizing antibodies","date":"2017-03-13","authors":["Michael B Doud","Scott E Hensley","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1006271","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006271","image":"/assets/papers/2017_doud.png","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2017_doud.md","filePath":"papers/2017_doud.md"}'),o={name:"papers/2017_doud.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Identifying viral mutations that confer escape from antibodies is crucial for understanding the interplay between immunity and viral evolution. We describe a high-throughput approach to quantify the selection that monoclonal antibodies exert on all single amino-acid mutations to a viral protein. This approach, mutational antigenic profiling, involves creating all replication-competent protein variants of a virus, selecting with antibody, and using deep sequencing to identify enriched mutations. We use mutational antigenic profiling to comprehensively identify mutations that enable influenza virus to escape four monoclonal antibodies targeting hemagglutinin, and validate key findings with neutralization assays. We find remarkable mutation-level idiosyncrasy in antibody escape: for instance, at a single residue targeted by two antibodies, some mutations escape both antibodies while other mutations escape only one or the other. Because mutational antigenic profiling rapidly maps all mutations selected by an antibody, it is useful for elucidating immune specificities and interpreting the antigenic consequences of viral genetic variation.",-1),l=[s,r];function c(d,p,u,m,h,g){return i(),t("div",null,l)}const _=a(o,[["render",c]]);export{b as __pageData,_ as default}; +import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Complete mapping of viral escape from neutralizing antibodies","description":"","frontmatter":{"layout":"paper","title":"Complete mapping of viral escape from neutralizing antibodies","date":"2017-03-13","authors":["Michael B Doud","Scott E Hensley","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1006271","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006271","image":"/assets/papers/2017_doud.png","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2017_doud.md","filePath":"papers/2017_doud.md"}'),o={name:"papers/2017_doud.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Identifying viral mutations that confer escape from antibodies is crucial for understanding the interplay between immunity and viral evolution. We describe a high-throughput approach to quantify the selection that monoclonal antibodies exert on all single amino-acid mutations to a viral protein. This approach, mutational antigenic profiling, involves creating all replication-competent protein variants of a virus, selecting with antibody, and using deep sequencing to identify enriched mutations. We use mutational antigenic profiling to comprehensively identify mutations that enable influenza virus to escape four monoclonal antibodies targeting hemagglutinin, and validate key findings with neutralization assays. We find remarkable mutation-level idiosyncrasy in antibody escape: for instance, at a single residue targeted by two antibodies, some mutations escape both antibodies while other mutations escape only one or the other. Because mutational antigenic profiling rapidly maps all mutations selected by an antibody, it is useful for elucidating immune specificities and interpreting the antigenic consequences of viral genetic variation.",-1),l=[s,r];function c(d,p,u,m,h,g){return i(),t("div",null,l)}const _=a(o,[["render",c]]);export{b as __pageData,_ as default}; diff --git a/assets/papers_2017_doud.md.AtVhWQrn.lean.js b/assets/papers_2017_doud.md.CIblnIx8.lean.js similarity index 97% rename from assets/papers_2017_doud.md.AtVhWQrn.lean.js rename to assets/papers_2017_doud.md.CIblnIx8.lean.js index bd798b6..be7bc90 100644 --- a/assets/papers_2017_doud.md.AtVhWQrn.lean.js +++ b/assets/papers_2017_doud.md.CIblnIx8.lean.js @@ -1 +1 @@ -import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Complete mapping of viral escape from neutralizing antibodies","description":"","frontmatter":{"layout":"paper","title":"Complete mapping of viral escape from neutralizing antibodies","date":"2017-03-13","authors":["Michael B Doud","Scott E Hensley","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1006271","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006271","image":"/assets/papers/2017_doud.png","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2017_doud.md","filePath":"papers/2017_doud.md"}'),o={name:"papers/2017_doud.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Identifying viral mutations that confer escape from antibodies is crucial for understanding the interplay between immunity and viral evolution. We describe a high-throughput approach to quantify the selection that monoclonal antibodies exert on all single amino-acid mutations to a viral protein. This approach, mutational antigenic profiling, involves creating all replication-competent protein variants of a virus, selecting with antibody, and using deep sequencing to identify enriched mutations. We use mutational antigenic profiling to comprehensively identify mutations that enable influenza virus to escape four monoclonal antibodies targeting hemagglutinin, and validate key findings with neutralization assays. We find remarkable mutation-level idiosyncrasy in antibody escape: for instance, at a single residue targeted by two antibodies, some mutations escape both antibodies while other mutations escape only one or the other. Because mutational antigenic profiling rapidly maps all mutations selected by an antibody, it is useful for elucidating immune specificities and interpreting the antigenic consequences of viral genetic variation.",-1),l=[s,r];function c(d,p,u,m,h,g){return i(),t("div",null,l)}const _=a(o,[["render",c]]);export{b as __pageData,_ as default}; +import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Complete mapping of viral escape from neutralizing antibodies","description":"","frontmatter":{"layout":"paper","title":"Complete mapping of viral escape from neutralizing antibodies","date":"2017-03-13","authors":["Michael B Doud","Scott E Hensley","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1006271","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006271","image":"/assets/papers/2017_doud.png","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2017_doud.md","filePath":"papers/2017_doud.md"}'),o={name:"papers/2017_doud.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Identifying viral mutations that confer escape from antibodies is crucial for understanding the interplay between immunity and viral evolution. We describe a high-throughput approach to quantify the selection that monoclonal antibodies exert on all single amino-acid mutations to a viral protein. This approach, mutational antigenic profiling, involves creating all replication-competent protein variants of a virus, selecting with antibody, and using deep sequencing to identify enriched mutations. We use mutational antigenic profiling to comprehensively identify mutations that enable influenza virus to escape four monoclonal antibodies targeting hemagglutinin, and validate key findings with neutralization assays. We find remarkable mutation-level idiosyncrasy in antibody escape: for instance, at a single residue targeted by two antibodies, some mutations escape both antibodies while other mutations escape only one or the other. Because mutational antigenic profiling rapidly maps all mutations selected by an antibody, it is useful for elucidating immune specificities and interpreting the antigenic consequences of viral genetic variation.",-1),l=[s,r];function c(d,p,u,m,h,g){return i(),t("div",null,l)}const _=a(o,[["render",c]]);export{b as __pageData,_ as default}; diff --git a/assets/papers_2017_hilton.md.DC6yPOxn.js b/assets/papers_2017_hilton.md.CboQGh0y.js similarity index 97% rename from assets/papers_2017_hilton.md.DC6yPOxn.js rename to assets/papers_2017_hilton.md.CboQGh0y.js index 3cfb5a2..c67f713 100644 --- a/assets/papers_2017_hilton.md.DC6yPOxn.js +++ b/assets/papers_2017_hilton.md.CboQGh0y.js @@ -1 +1 @@ -import{_ as t,c as a,o as n,b as e,d as s}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"phydms: Software for phylogenetic analyses informed by deep mutational scanning","description":"","frontmatter":{"layout":"paper","title":"phydms: Software for phylogenetic analyses informed by deep mutational scanning","date":"2017-07-31","authors":["Sarah K Hilton","Michael B Doud","Jesse D Bloom"],"journal":"PeerJ","doi":"10.7717/peerj.3657","link":"https://peerj.com/articles/3657/","image":"/assets/papers/2017_hilton.jpg","keywords":["Phylogenetics","Software tools"]},"headers":[],"relativePath":"papers/2017_hilton.md","filePath":"papers/2017_hilton.md"}'),o={name:"papers/2017_hilton.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"It has recently become possible to experimentally measure the effects of all amino-acid point mutations to proteins using deep mutational scanning. These experimental measurements can inform site-specific phylogenetic substitution models of gene evolution in nature. Here we describe software that efficiently performs analyses with such substitution models. This software, phydms, can be used to compare the results of deep mutational scanning experiments to the selection on genes in nature. Given a phylogenetic tree topology inferred with another program, phydms enables rigorous comparison of how well different experiments on the same gene capture actual natural selection. It also enables re-scaling of deep mutational scanning data to account for differences in the stringency of selection in the lab and nature. Finally, phydms can identify sites that are evolving differently in nature than expected from experiments in the lab. As data from deep mutational scanning experiments become increasingly widespread, phydms will facilitate quantitative comparison of the experimental results to the actual selection pressures shaping evolution in nature.",-1),l=[i,r];function c(p,d,h,m,f,u){return n(),a("div",null,l)}const _=t(o,[["render",c]]);export{g as __pageData,_ as default}; +import{_ as t,c as a,o as n,b as e,d as s}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"phydms: Software for phylogenetic analyses informed by deep mutational scanning","description":"","frontmatter":{"layout":"paper","title":"phydms: Software for phylogenetic analyses informed by deep mutational scanning","date":"2017-07-31","authors":["Sarah K Hilton","Michael B Doud","Jesse D Bloom"],"journal":"PeerJ","doi":"10.7717/peerj.3657","link":"https://peerj.com/articles/3657/","image":"/assets/papers/2017_hilton.jpg","keywords":["Phylogenetics","Software tools"]},"headers":[],"relativePath":"papers/2017_hilton.md","filePath":"papers/2017_hilton.md"}'),o={name:"papers/2017_hilton.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"It has recently become possible to experimentally measure the effects of all amino-acid point mutations to proteins using deep mutational scanning. These experimental measurements can inform site-specific phylogenetic substitution models of gene evolution in nature. Here we describe software that efficiently performs analyses with such substitution models. This software, phydms, can be used to compare the results of deep mutational scanning experiments to the selection on genes in nature. Given a phylogenetic tree topology inferred with another program, phydms enables rigorous comparison of how well different experiments on the same gene capture actual natural selection. It also enables re-scaling of deep mutational scanning data to account for differences in the stringency of selection in the lab and nature. Finally, phydms can identify sites that are evolving differently in nature than expected from experiments in the lab. As data from deep mutational scanning experiments become increasingly widespread, phydms will facilitate quantitative comparison of the experimental results to the actual selection pressures shaping evolution in nature.",-1),l=[i,r];function c(p,d,h,m,f,u){return n(),a("div",null,l)}const _=t(o,[["render",c]]);export{g as __pageData,_ as default}; diff --git a/assets/papers_2017_hilton.md.DC6yPOxn.lean.js b/assets/papers_2017_hilton.md.CboQGh0y.lean.js similarity index 97% rename from assets/papers_2017_hilton.md.DC6yPOxn.lean.js rename to assets/papers_2017_hilton.md.CboQGh0y.lean.js index 3cfb5a2..c67f713 100644 --- a/assets/papers_2017_hilton.md.DC6yPOxn.lean.js +++ b/assets/papers_2017_hilton.md.CboQGh0y.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as n,b as e,d as s}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"phydms: Software for phylogenetic analyses informed by deep mutational scanning","description":"","frontmatter":{"layout":"paper","title":"phydms: Software for phylogenetic analyses informed by deep mutational scanning","date":"2017-07-31","authors":["Sarah K Hilton","Michael B Doud","Jesse D Bloom"],"journal":"PeerJ","doi":"10.7717/peerj.3657","link":"https://peerj.com/articles/3657/","image":"/assets/papers/2017_hilton.jpg","keywords":["Phylogenetics","Software tools"]},"headers":[],"relativePath":"papers/2017_hilton.md","filePath":"papers/2017_hilton.md"}'),o={name:"papers/2017_hilton.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"It has recently become possible to experimentally measure the effects of all amino-acid point mutations to proteins using deep mutational scanning. These experimental measurements can inform site-specific phylogenetic substitution models of gene evolution in nature. Here we describe software that efficiently performs analyses with such substitution models. This software, phydms, can be used to compare the results of deep mutational scanning experiments to the selection on genes in nature. Given a phylogenetic tree topology inferred with another program, phydms enables rigorous comparison of how well different experiments on the same gene capture actual natural selection. It also enables re-scaling of deep mutational scanning data to account for differences in the stringency of selection in the lab and nature. Finally, phydms can identify sites that are evolving differently in nature than expected from experiments in the lab. As data from deep mutational scanning experiments become increasingly widespread, phydms will facilitate quantitative comparison of the experimental results to the actual selection pressures shaping evolution in nature.",-1),l=[i,r];function c(p,d,h,m,f,u){return n(),a("div",null,l)}const _=t(o,[["render",c]]);export{g as __pageData,_ as default}; +import{_ as t,c as a,o as n,b as e,d as s}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"phydms: Software for phylogenetic analyses informed by deep mutational scanning","description":"","frontmatter":{"layout":"paper","title":"phydms: Software for phylogenetic analyses informed by deep mutational scanning","date":"2017-07-31","authors":["Sarah K Hilton","Michael B Doud","Jesse D Bloom"],"journal":"PeerJ","doi":"10.7717/peerj.3657","link":"https://peerj.com/articles/3657/","image":"/assets/papers/2017_hilton.jpg","keywords":["Phylogenetics","Software tools"]},"headers":[],"relativePath":"papers/2017_hilton.md","filePath":"papers/2017_hilton.md"}'),o={name:"papers/2017_hilton.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"It has recently become possible to experimentally measure the effects of all amino-acid point mutations to proteins using deep mutational scanning. These experimental measurements can inform site-specific phylogenetic substitution models of gene evolution in nature. Here we describe software that efficiently performs analyses with such substitution models. This software, phydms, can be used to compare the results of deep mutational scanning experiments to the selection on genes in nature. Given a phylogenetic tree topology inferred with another program, phydms enables rigorous comparison of how well different experiments on the same gene capture actual natural selection. It also enables re-scaling of deep mutational scanning data to account for differences in the stringency of selection in the lab and nature. Finally, phydms can identify sites that are evolving differently in nature than expected from experiments in the lab. As data from deep mutational scanning experiments become increasingly widespread, phydms will facilitate quantitative comparison of the experimental results to the actual selection pressures shaping evolution in nature.",-1),l=[i,r];function c(p,d,h,m,f,u){return n(),a("div",null,l)}const _=t(o,[["render",c]]);export{g as __pageData,_ as default}; diff --git a/assets/papers_2017_xue.md.9e9gI7Aj.js b/assets/papers_2017_xue.md.DskBsQGR.js similarity index 97% rename from assets/papers_2017_xue.md.9e9gI7Aj.js rename to assets/papers_2017_xue.md.DskBsQGR.js index 856fe92..eea2a60 100644 --- a/assets/papers_2017_xue.md.9e9gI7Aj.js +++ b/assets/papers_2017_xue.md.DskBsQGR.js @@ -1 +1 @@ -import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Parallel evolution of influenza across multiple spatiotemporal scales","description":"","frontmatter":{"layout":"paper","title":"Parallel evolution of influenza across multiple spatiotemporal scales","date":"2017-06-27","authors":["Katherine S Xue","Terry Stevens-Ayers","Angela P Campbell","Janet A Englund","Steven A Pergam","Michael Boeckh","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.26875.001","link":"https://elifesciences.org/articles/26875","image":"/assets/papers/2017_xue.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2017_xue.md","filePath":"papers/2017_xue.md"}'),s={name:"papers/2017_xue.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),l=e("p",null,"Viral variants that arise in the global influenza population begin as de novo mutations in single infected hosts, but the evolutionary dynamics that transform within-host variation to global genetic diversity are poorly understood. Here, we demonstrate that influenza evolution within infected humans recapitulates many evolutionary dynamics observed at the global scale. We deep-sequence longitudinal samples from four immunocompromised patients with long-term H3N2 influenza infections. We find parallel evolution across three scales: within individual patients, in different patients in our study, and in the global influenza population. In hemagglutinin, a small set of mutations arises independently in multiple patients. These same mutations emerge repeatedly within single patients and compete with one another, providing a vivid clinical example of clonal interference. Many of these recurrent within-host mutations also reach a high global frequency in the decade following the patient infections. Our results demonstrate surprising concordance in evolutionary dynamics across multiple spatiotemporal scales.",-1),r=[o,l];function c(u,p,d,h,m,f){return n(),a("div",null,r)}const v=t(s,[["render",c]]);export{_ as __pageData,v as default}; +import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Parallel evolution of influenza across multiple spatiotemporal scales","description":"","frontmatter":{"layout":"paper","title":"Parallel evolution of influenza across multiple spatiotemporal scales","date":"2017-06-27","authors":["Katherine S Xue","Terry Stevens-Ayers","Angela P Campbell","Janet A Englund","Steven A Pergam","Michael Boeckh","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.26875.001","link":"https://elifesciences.org/articles/26875","image":"/assets/papers/2017_xue.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2017_xue.md","filePath":"papers/2017_xue.md"}'),s={name:"papers/2017_xue.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),l=e("p",null,"Viral variants that arise in the global influenza population begin as de novo mutations in single infected hosts, but the evolutionary dynamics that transform within-host variation to global genetic diversity are poorly understood. Here, we demonstrate that influenza evolution within infected humans recapitulates many evolutionary dynamics observed at the global scale. We deep-sequence longitudinal samples from four immunocompromised patients with long-term H3N2 influenza infections. We find parallel evolution across three scales: within individual patients, in different patients in our study, and in the global influenza population. In hemagglutinin, a small set of mutations arises independently in multiple patients. These same mutations emerge repeatedly within single patients and compete with one another, providing a vivid clinical example of clonal interference. Many of these recurrent within-host mutations also reach a high global frequency in the decade following the patient infections. Our results demonstrate surprising concordance in evolutionary dynamics across multiple spatiotemporal scales.",-1),r=[o,l];function c(u,p,d,h,m,f){return n(),a("div",null,r)}const v=t(s,[["render",c]]);export{_ as __pageData,v as default}; diff --git a/assets/papers_2017_xue.md.9e9gI7Aj.lean.js b/assets/papers_2017_xue.md.DskBsQGR.lean.js similarity index 97% rename from assets/papers_2017_xue.md.9e9gI7Aj.lean.js rename to assets/papers_2017_xue.md.DskBsQGR.lean.js index 856fe92..eea2a60 100644 --- a/assets/papers_2017_xue.md.9e9gI7Aj.lean.js +++ b/assets/papers_2017_xue.md.DskBsQGR.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Parallel evolution of influenza across multiple spatiotemporal scales","description":"","frontmatter":{"layout":"paper","title":"Parallel evolution of influenza across multiple spatiotemporal scales","date":"2017-06-27","authors":["Katherine S Xue","Terry Stevens-Ayers","Angela P Campbell","Janet A Englund","Steven A Pergam","Michael Boeckh","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.26875.001","link":"https://elifesciences.org/articles/26875","image":"/assets/papers/2017_xue.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2017_xue.md","filePath":"papers/2017_xue.md"}'),s={name:"papers/2017_xue.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),l=e("p",null,"Viral variants that arise in the global influenza population begin as de novo mutations in single infected hosts, but the evolutionary dynamics that transform within-host variation to global genetic diversity are poorly understood. Here, we demonstrate that influenza evolution within infected humans recapitulates many evolutionary dynamics observed at the global scale. We deep-sequence longitudinal samples from four immunocompromised patients with long-term H3N2 influenza infections. We find parallel evolution across three scales: within individual patients, in different patients in our study, and in the global influenza population. In hemagglutinin, a small set of mutations arises independently in multiple patients. These same mutations emerge repeatedly within single patients and compete with one another, providing a vivid clinical example of clonal interference. Many of these recurrent within-host mutations also reach a high global frequency in the decade following the patient infections. Our results demonstrate surprising concordance in evolutionary dynamics across multiple spatiotemporal scales.",-1),r=[o,l];function c(u,p,d,h,m,f){return n(),a("div",null,r)}const v=t(s,[["render",c]]);export{_ as __pageData,v as default}; +import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Parallel evolution of influenza across multiple spatiotemporal scales","description":"","frontmatter":{"layout":"paper","title":"Parallel evolution of influenza across multiple spatiotemporal scales","date":"2017-06-27","authors":["Katherine S Xue","Terry Stevens-Ayers","Angela P Campbell","Janet A Englund","Steven A Pergam","Michael Boeckh","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.26875.001","link":"https://elifesciences.org/articles/26875","image":"/assets/papers/2017_xue.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2017_xue.md","filePath":"papers/2017_xue.md"}'),s={name:"papers/2017_xue.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),l=e("p",null,"Viral variants that arise in the global influenza population begin as de novo mutations in single infected hosts, but the evolutionary dynamics that transform within-host variation to global genetic diversity are poorly understood. Here, we demonstrate that influenza evolution within infected humans recapitulates many evolutionary dynamics observed at the global scale. We deep-sequence longitudinal samples from four immunocompromised patients with long-term H3N2 influenza infections. We find parallel evolution across three scales: within individual patients, in different patients in our study, and in the global influenza population. In hemagglutinin, a small set of mutations arises independently in multiple patients. These same mutations emerge repeatedly within single patients and compete with one another, providing a vivid clinical example of clonal interference. Many of these recurrent within-host mutations also reach a high global frequency in the decade following the patient infections. Our results demonstrate surprising concordance in evolutionary dynamics across multiple spatiotemporal scales.",-1),r=[o,l];function c(u,p,d,h,m,f){return n(),a("div",null,r)}const v=t(s,[["render",c]]);export{_ as __pageData,v as default}; diff --git a/assets/papers_2018_dingens.md.27Wcex-O.js b/assets/papers_2018_dingens.md.D5n97hEY.js similarity index 97% rename from assets/papers_2018_dingens.md.27Wcex-O.js rename to assets/papers_2018_dingens.md.D5n97hEY.js index 32f6d88..95c3fda 100644 --- a/assets/papers_2018_dingens.md.27Wcex-O.js +++ b/assets/papers_2018_dingens.md.D5n97hEY.js @@ -1 +1 @@ -import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV","description":"","frontmatter":{"layout":"paper","title":"Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV","date":"2018-07-05","authors":["Adam S Dingens","Priyamvada Acharya","Hugh K Haddox","Reda Rawi","Kai Xu","Gwo-Yu Chuang","Hui Wei","Baoshan Zhang","John R Mascola","Bridget Carragher","Clinton S Potter","Julie Overbaugh","Peter D Kwong","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1007159","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007159","image":"/assets/papers/2018_dingens.png","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2018_dingens.md","filePath":"papers/2018_dingens.md"}'),o={name:"papers/2018_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Eliciting broadly neutralizing antibodies (bnAbs) targeting envelope (Env) is a major goal of HIV vaccine development, but cross-clade breadth from immunization has only sporadically been observed. Recently, Xu et al (2018) elicited cross-reactive neutralizing antibody responses in a variety of animal models using immunogens based on the epitope of bnAb VRC34.01. The VRC34.01 antibody, which was elicited by natural human infection, targets the N terminus of the Env fusion peptide, a critical component of the virus entry machinery. Here we precisely characterize the functional epitopes of VRC34.01 and two vaccine-elicited murine antibodies by mapping all single amino-acid mutations to the BG505 Env that affect viral neutralization. While escape from VRC34.01 occurred via mutations in both fusion peptide and distal interacting sites of the Env trimer, escape from the vaccine-elicited antibodies was mediated predominantly by mutations in the fusion peptide. Cryo-electron microscopy of four vaccine-elicited antibodies in complex with Env trimer revealed focused recognition of the fusion peptide and provided a structural basis for development of neutralization breadth. Together, these functional and structural data suggest that the breadth of vaccine-elicited antibodies targeting the fusion peptide can be enhanced by specific interactions with additional portions of Env. Thus, our complete maps of viral escape both delineate pathways of resistance to these fusion peptide-directed antibodies and provide a strategy to improve the breadth or potency of future vaccine-induced antibodies against Env’s fusion peptide.",-1),c=[s,r];function d(p,l,u,h,f,m){return i(),a("div",null,c)}const v=t(o,[["render",d]]);export{b as __pageData,v as default}; +import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV","description":"","frontmatter":{"layout":"paper","title":"Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV","date":"2018-07-05","authors":["Adam S Dingens","Priyamvada Acharya","Hugh K Haddox","Reda Rawi","Kai Xu","Gwo-Yu Chuang","Hui Wei","Baoshan Zhang","John R Mascola","Bridget Carragher","Clinton S Potter","Julie Overbaugh","Peter D Kwong","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1007159","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007159","image":"/assets/papers/2018_dingens.png","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2018_dingens.md","filePath":"papers/2018_dingens.md"}'),o={name:"papers/2018_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Eliciting broadly neutralizing antibodies (bnAbs) targeting envelope (Env) is a major goal of HIV vaccine development, but cross-clade breadth from immunization has only sporadically been observed. Recently, Xu et al (2018) elicited cross-reactive neutralizing antibody responses in a variety of animal models using immunogens based on the epitope of bnAb VRC34.01. The VRC34.01 antibody, which was elicited by natural human infection, targets the N terminus of the Env fusion peptide, a critical component of the virus entry machinery. Here we precisely characterize the functional epitopes of VRC34.01 and two vaccine-elicited murine antibodies by mapping all single amino-acid mutations to the BG505 Env that affect viral neutralization. While escape from VRC34.01 occurred via mutations in both fusion peptide and distal interacting sites of the Env trimer, escape from the vaccine-elicited antibodies was mediated predominantly by mutations in the fusion peptide. Cryo-electron microscopy of four vaccine-elicited antibodies in complex with Env trimer revealed focused recognition of the fusion peptide and provided a structural basis for development of neutralization breadth. Together, these functional and structural data suggest that the breadth of vaccine-elicited antibodies targeting the fusion peptide can be enhanced by specific interactions with additional portions of Env. Thus, our complete maps of viral escape both delineate pathways of resistance to these fusion peptide-directed antibodies and provide a strategy to improve the breadth or potency of future vaccine-induced antibodies against Env’s fusion peptide.",-1),c=[s,r];function d(p,l,u,h,f,m){return i(),a("div",null,c)}const v=t(o,[["render",d]]);export{b as __pageData,v as default}; diff --git a/assets/papers_2018_dingens.md.27Wcex-O.lean.js b/assets/papers_2018_dingens.md.D5n97hEY.lean.js similarity index 97% rename from assets/papers_2018_dingens.md.27Wcex-O.lean.js rename to assets/papers_2018_dingens.md.D5n97hEY.lean.js index 32f6d88..95c3fda 100644 --- a/assets/papers_2018_dingens.md.27Wcex-O.lean.js +++ b/assets/papers_2018_dingens.md.D5n97hEY.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV","description":"","frontmatter":{"layout":"paper","title":"Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV","date":"2018-07-05","authors":["Adam S Dingens","Priyamvada Acharya","Hugh K Haddox","Reda Rawi","Kai Xu","Gwo-Yu Chuang","Hui Wei","Baoshan Zhang","John R Mascola","Bridget Carragher","Clinton S Potter","Julie Overbaugh","Peter D Kwong","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1007159","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007159","image":"/assets/papers/2018_dingens.png","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2018_dingens.md","filePath":"papers/2018_dingens.md"}'),o={name:"papers/2018_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Eliciting broadly neutralizing antibodies (bnAbs) targeting envelope (Env) is a major goal of HIV vaccine development, but cross-clade breadth from immunization has only sporadically been observed. Recently, Xu et al (2018) elicited cross-reactive neutralizing antibody responses in a variety of animal models using immunogens based on the epitope of bnAb VRC34.01. The VRC34.01 antibody, which was elicited by natural human infection, targets the N terminus of the Env fusion peptide, a critical component of the virus entry machinery. Here we precisely characterize the functional epitopes of VRC34.01 and two vaccine-elicited murine antibodies by mapping all single amino-acid mutations to the BG505 Env that affect viral neutralization. While escape from VRC34.01 occurred via mutations in both fusion peptide and distal interacting sites of the Env trimer, escape from the vaccine-elicited antibodies was mediated predominantly by mutations in the fusion peptide. Cryo-electron microscopy of four vaccine-elicited antibodies in complex with Env trimer revealed focused recognition of the fusion peptide and provided a structural basis for development of neutralization breadth. Together, these functional and structural data suggest that the breadth of vaccine-elicited antibodies targeting the fusion peptide can be enhanced by specific interactions with additional portions of Env. Thus, our complete maps of viral escape both delineate pathways of resistance to these fusion peptide-directed antibodies and provide a strategy to improve the breadth or potency of future vaccine-induced antibodies against Env’s fusion peptide.",-1),c=[s,r];function d(p,l,u,h,f,m){return i(),a("div",null,c)}const v=t(o,[["render",d]]);export{b as __pageData,v as default}; +import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV","description":"","frontmatter":{"layout":"paper","title":"Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV","date":"2018-07-05","authors":["Adam S Dingens","Priyamvada Acharya","Hugh K Haddox","Reda Rawi","Kai Xu","Gwo-Yu Chuang","Hui Wei","Baoshan Zhang","John R Mascola","Bridget Carragher","Clinton S Potter","Julie Overbaugh","Peter D Kwong","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1007159","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007159","image":"/assets/papers/2018_dingens.png","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2018_dingens.md","filePath":"papers/2018_dingens.md"}'),o={name:"papers/2018_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Eliciting broadly neutralizing antibodies (bnAbs) targeting envelope (Env) is a major goal of HIV vaccine development, but cross-clade breadth from immunization has only sporadically been observed. Recently, Xu et al (2018) elicited cross-reactive neutralizing antibody responses in a variety of animal models using immunogens based on the epitope of bnAb VRC34.01. The VRC34.01 antibody, which was elicited by natural human infection, targets the N terminus of the Env fusion peptide, a critical component of the virus entry machinery. Here we precisely characterize the functional epitopes of VRC34.01 and two vaccine-elicited murine antibodies by mapping all single amino-acid mutations to the BG505 Env that affect viral neutralization. While escape from VRC34.01 occurred via mutations in both fusion peptide and distal interacting sites of the Env trimer, escape from the vaccine-elicited antibodies was mediated predominantly by mutations in the fusion peptide. Cryo-electron microscopy of four vaccine-elicited antibodies in complex with Env trimer revealed focused recognition of the fusion peptide and provided a structural basis for development of neutralization breadth. Together, these functional and structural data suggest that the breadth of vaccine-elicited antibodies targeting the fusion peptide can be enhanced by specific interactions with additional portions of Env. Thus, our complete maps of viral escape both delineate pathways of resistance to these fusion peptide-directed antibodies and provide a strategy to improve the breadth or potency of future vaccine-induced antibodies against Env’s fusion peptide.",-1),c=[s,r];function d(p,l,u,h,f,m){return i(),a("div",null,c)}const v=t(o,[["render",d]]);export{b as __pageData,v as default}; diff --git a/assets/papers_2018_doud.md.Qlm__c6R.js b/assets/papers_2018_doud.md.mfpzn1GV.js similarity index 97% rename from assets/papers_2018_doud.md.Qlm__c6R.js rename to assets/papers_2018_doud.md.mfpzn1GV.js index ac02dbf..ba26b8c 100644 --- a/assets/papers_2018_doud.md.Qlm__c6R.js +++ b/assets/papers_2018_doud.md.mfpzn1GV.js @@ -1 +1 @@ -import{_ as a,c as t,o as i,b as e,d as s}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin","date":"2018-04-11","authors":["Michael B Doud*","Juhye M Lee*","Jesse D Bloom"],"journal":"Nature communications","doi":"10.1038/s41467-018-03665-3","link":"https://www.nature.com/articles/s41467-018-03665-3","image":"/assets/papers/2018_doud.jpg","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2018_doud.md","filePath":"papers/2018_doud.md"}'),n={name:"papers/2018_doud.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza virus can escape most antibodies with single mutations. However, rare antibodies broadly neutralize many viral strains. It is unclear how easily influenza virus might escape such antibodies if there was strong pressure to do so. Here, we map all single amino-acid mutations that increase resistance to broad antibodies to H1 hemagglutinin. Our approach not only identifies antigenic mutations but also quantifies their effect sizes. All antibodies select mutations, but the effect sizes vary widely. The virus can escape a broad antibody to hemagglutinin’s receptor-binding site the same way it escapes narrow strain-specific antibodies: via single mutations with huge effects. In contrast, broad antibodies to hemagglutinin’s stalk only select mutations with small effects. Therefore, among the antibodies we examine, breadth is an imperfect indicator of the potential for viral escape via single mutations. Antibodies targeting the H1 hemagglutinin stalk are quantifiably harder to escape than the other antibodies tested here.",-1),l=[o,r];function c(d,u,h,m,p,f){return i(),t("div",null,l)}const _=a(n,[["render",c]]);export{g as __pageData,_ as default}; +import{_ as a,c as t,o as i,b as e,d as s}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin","date":"2018-04-11","authors":["Michael B Doud*","Juhye M Lee*","Jesse D Bloom"],"journal":"Nature communications","doi":"10.1038/s41467-018-03665-3","link":"https://www.nature.com/articles/s41467-018-03665-3","image":"/assets/papers/2018_doud.jpg","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2018_doud.md","filePath":"papers/2018_doud.md"}'),n={name:"papers/2018_doud.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza virus can escape most antibodies with single mutations. However, rare antibodies broadly neutralize many viral strains. It is unclear how easily influenza virus might escape such antibodies if there was strong pressure to do so. Here, we map all single amino-acid mutations that increase resistance to broad antibodies to H1 hemagglutinin. Our approach not only identifies antigenic mutations but also quantifies their effect sizes. All antibodies select mutations, but the effect sizes vary widely. The virus can escape a broad antibody to hemagglutinin’s receptor-binding site the same way it escapes narrow strain-specific antibodies: via single mutations with huge effects. In contrast, broad antibodies to hemagglutinin’s stalk only select mutations with small effects. Therefore, among the antibodies we examine, breadth is an imperfect indicator of the potential for viral escape via single mutations. Antibodies targeting the H1 hemagglutinin stalk are quantifiably harder to escape than the other antibodies tested here.",-1),l=[o,r];function c(d,u,h,m,p,f){return i(),t("div",null,l)}const _=a(n,[["render",c]]);export{g as __pageData,_ as default}; diff --git a/assets/papers_2018_doud.md.Qlm__c6R.lean.js b/assets/papers_2018_doud.md.mfpzn1GV.lean.js similarity index 97% rename from assets/papers_2018_doud.md.Qlm__c6R.lean.js rename to assets/papers_2018_doud.md.mfpzn1GV.lean.js index ac02dbf..ba26b8c 100644 --- a/assets/papers_2018_doud.md.Qlm__c6R.lean.js +++ b/assets/papers_2018_doud.md.mfpzn1GV.lean.js @@ -1 +1 @@ -import{_ as a,c as t,o as i,b as e,d as s}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin","date":"2018-04-11","authors":["Michael B Doud*","Juhye M Lee*","Jesse D Bloom"],"journal":"Nature communications","doi":"10.1038/s41467-018-03665-3","link":"https://www.nature.com/articles/s41467-018-03665-3","image":"/assets/papers/2018_doud.jpg","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2018_doud.md","filePath":"papers/2018_doud.md"}'),n={name:"papers/2018_doud.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza virus can escape most antibodies with single mutations. However, rare antibodies broadly neutralize many viral strains. It is unclear how easily influenza virus might escape such antibodies if there was strong pressure to do so. Here, we map all single amino-acid mutations that increase resistance to broad antibodies to H1 hemagglutinin. Our approach not only identifies antigenic mutations but also quantifies their effect sizes. All antibodies select mutations, but the effect sizes vary widely. The virus can escape a broad antibody to hemagglutinin’s receptor-binding site the same way it escapes narrow strain-specific antibodies: via single mutations with huge effects. In contrast, broad antibodies to hemagglutinin’s stalk only select mutations with small effects. Therefore, among the antibodies we examine, breadth is an imperfect indicator of the potential for viral escape via single mutations. Antibodies targeting the H1 hemagglutinin stalk are quantifiably harder to escape than the other antibodies tested here.",-1),l=[o,r];function c(d,u,h,m,p,f){return i(),t("div",null,l)}const _=a(n,[["render",c]]);export{g as __pageData,_ as default}; +import{_ as a,c as t,o as i,b as e,d as s}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin","date":"2018-04-11","authors":["Michael B Doud*","Juhye M Lee*","Jesse D Bloom"],"journal":"Nature communications","doi":"10.1038/s41467-018-03665-3","link":"https://www.nature.com/articles/s41467-018-03665-3","image":"/assets/papers/2018_doud.jpg","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2018_doud.md","filePath":"papers/2018_doud.md"}'),n={name:"papers/2018_doud.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza virus can escape most antibodies with single mutations. However, rare antibodies broadly neutralize many viral strains. It is unclear how easily influenza virus might escape such antibodies if there was strong pressure to do so. Here, we map all single amino-acid mutations that increase resistance to broad antibodies to H1 hemagglutinin. Our approach not only identifies antigenic mutations but also quantifies their effect sizes. All antibodies select mutations, but the effect sizes vary widely. The virus can escape a broad antibody to hemagglutinin’s receptor-binding site the same way it escapes narrow strain-specific antibodies: via single mutations with huge effects. In contrast, broad antibodies to hemagglutinin’s stalk only select mutations with small effects. Therefore, among the antibodies we examine, breadth is an imperfect indicator of the potential for viral escape via single mutations. Antibodies targeting the H1 hemagglutinin stalk are quantifiably harder to escape than the other antibodies tested here.",-1),l=[o,r];function c(d,u,h,m,p,f){return i(),t("div",null,l)}const _=a(n,[["render",c]]);export{g as __pageData,_ as default}; diff --git a/assets/papers_2018_haddox.md.JLNADHBx.js b/assets/papers_2018_haddox.md.-EzsKUxl.js similarity index 96% rename from assets/papers_2018_haddox.md.JLNADHBx.js rename to assets/papers_2018_haddox.md.-EzsKUxl.js index bbbcb35..e39edcb 100644 --- a/assets/papers_2018_haddox.md.JLNADHBx.js +++ b/assets/papers_2018_haddox.md.-EzsKUxl.js @@ -1 +1 @@ -import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Mapping mutational effects along the evolutionary landscape of HIV envelope","description":"","frontmatter":{"layout":"paper","title":"Mapping mutational effects along the evolutionary landscape of HIV envelope","date":"2018-03-28","authors":["Hugh K Haddox*","Adam S Dingens*","Sarah K Hilton","Julie Overbaugh","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.34420","link":"https://elifesciences.org/articles/34420","image":"/assets/papers/2018_haddox.jpg","keywords":["HIV","Deep mutational scanning","Epistasis"]},"headers":[],"relativePath":"papers/2018_haddox.md","filePath":"papers/2018_haddox.md"}'),o={name:"papers/2018_haddox.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The immediate evolutionary space accessible to HIV is largely determined by how single amino acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here, we quantify the effects on viral growth of all amino acid mutations to two HIV envelope (Env) proteins that differ at > 100 residues. Most mutations similarly affect both Envs, but the amino acid preferences of a minority of sites have clearly shifted. These shifted sites usually prefer a specific amino acid in one Env, but tolerate many amino acids in the other. Surprisingly, shifts are only slightly enriched at sites that have substituted between the Envs—and many occur at residues that do not even contact substitutions. Therefore, long-range epistasis can unpredictably shift Env’s mutational tolerance during HIV evolution, although the amino acid preferences of most sites are conserved between moderately diverged viral strains.",-1),l=[n,r];function c(d,h,f,p,u,m){return s(),a("div",null,l)}const g=t(o,[["render",c]]);export{_ as __pageData,g as default}; +import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Mapping mutational effects along the evolutionary landscape of HIV envelope","description":"","frontmatter":{"layout":"paper","title":"Mapping mutational effects along the evolutionary landscape of HIV envelope","date":"2018-03-28","authors":["Hugh K Haddox*","Adam S Dingens*","Sarah K Hilton","Julie Overbaugh","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.34420","link":"https://elifesciences.org/articles/34420","image":"/assets/papers/2018_haddox.jpg","keywords":["HIV","Deep mutational scanning","Epistasis"]},"headers":[],"relativePath":"papers/2018_haddox.md","filePath":"papers/2018_haddox.md"}'),o={name:"papers/2018_haddox.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The immediate evolutionary space accessible to HIV is largely determined by how single amino acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here, we quantify the effects on viral growth of all amino acid mutations to two HIV envelope (Env) proteins that differ at > 100 residues. Most mutations similarly affect both Envs, but the amino acid preferences of a minority of sites have clearly shifted. These shifted sites usually prefer a specific amino acid in one Env, but tolerate many amino acids in the other. Surprisingly, shifts are only slightly enriched at sites that have substituted between the Envs—and many occur at residues that do not even contact substitutions. Therefore, long-range epistasis can unpredictably shift Env’s mutational tolerance during HIV evolution, although the amino acid preferences of most sites are conserved between moderately diverged viral strains.",-1),l=[n,r];function c(d,h,f,p,u,m){return s(),a("div",null,l)}const g=t(o,[["render",c]]);export{_ as __pageData,g as default}; diff --git a/assets/papers_2018_haddox.md.JLNADHBx.lean.js b/assets/papers_2018_haddox.md.-EzsKUxl.lean.js similarity index 96% rename from assets/papers_2018_haddox.md.JLNADHBx.lean.js rename to assets/papers_2018_haddox.md.-EzsKUxl.lean.js index bbbcb35..e39edcb 100644 --- a/assets/papers_2018_haddox.md.JLNADHBx.lean.js +++ b/assets/papers_2018_haddox.md.-EzsKUxl.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Mapping mutational effects along the evolutionary landscape of HIV envelope","description":"","frontmatter":{"layout":"paper","title":"Mapping mutational effects along the evolutionary landscape of HIV envelope","date":"2018-03-28","authors":["Hugh K Haddox*","Adam S Dingens*","Sarah K Hilton","Julie Overbaugh","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.34420","link":"https://elifesciences.org/articles/34420","image":"/assets/papers/2018_haddox.jpg","keywords":["HIV","Deep mutational scanning","Epistasis"]},"headers":[],"relativePath":"papers/2018_haddox.md","filePath":"papers/2018_haddox.md"}'),o={name:"papers/2018_haddox.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The immediate evolutionary space accessible to HIV is largely determined by how single amino acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here, we quantify the effects on viral growth of all amino acid mutations to two HIV envelope (Env) proteins that differ at > 100 residues. Most mutations similarly affect both Envs, but the amino acid preferences of a minority of sites have clearly shifted. These shifted sites usually prefer a specific amino acid in one Env, but tolerate many amino acids in the other. Surprisingly, shifts are only slightly enriched at sites that have substituted between the Envs—and many occur at residues that do not even contact substitutions. Therefore, long-range epistasis can unpredictably shift Env’s mutational tolerance during HIV evolution, although the amino acid preferences of most sites are conserved between moderately diverged viral strains.",-1),l=[n,r];function c(d,h,f,p,u,m){return s(),a("div",null,l)}const g=t(o,[["render",c]]);export{_ as __pageData,g as default}; +import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Mapping mutational effects along the evolutionary landscape of HIV envelope","description":"","frontmatter":{"layout":"paper","title":"Mapping mutational effects along the evolutionary landscape of HIV envelope","date":"2018-03-28","authors":["Hugh K Haddox*","Adam S Dingens*","Sarah K Hilton","Julie Overbaugh","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.34420","link":"https://elifesciences.org/articles/34420","image":"/assets/papers/2018_haddox.jpg","keywords":["HIV","Deep mutational scanning","Epistasis"]},"headers":[],"relativePath":"papers/2018_haddox.md","filePath":"papers/2018_haddox.md"}'),o={name:"papers/2018_haddox.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The immediate evolutionary space accessible to HIV is largely determined by how single amino acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here, we quantify the effects on viral growth of all amino acid mutations to two HIV envelope (Env) proteins that differ at > 100 residues. Most mutations similarly affect both Envs, but the amino acid preferences of a minority of sites have clearly shifted. These shifted sites usually prefer a specific amino acid in one Env, but tolerate many amino acids in the other. Surprisingly, shifts are only slightly enriched at sites that have substituted between the Envs—and many occur at residues that do not even contact substitutions. Therefore, long-range epistasis can unpredictably shift Env’s mutational tolerance during HIV evolution, although the amino acid preferences of most sites are conserved between moderately diverged viral strains.",-1),l=[n,r];function c(d,h,f,p,u,m){return s(),a("div",null,l)}const g=t(o,[["render",c]]);export{_ as __pageData,g as default}; diff --git a/assets/papers_2018_hilton.md.CFmlgqC8.js b/assets/papers_2018_hilton.md.C49rLQnc.js similarity index 97% rename from assets/papers_2018_hilton.md.CFmlgqC8.js rename to assets/papers_2018_hilton.md.C49rLQnc.js index 3bef7c7..2dec249 100644 --- a/assets/papers_2018_hilton.md.CFmlgqC8.js +++ b/assets/papers_2018_hilton.md.C49rLQnc.js @@ -1 +1 @@ -import{_ as t,c as i,o as s,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const v=JSON.parse('{"title":"Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence","description":"","frontmatter":{"layout":"paper","title":"Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence","date":"2018-07-01","authors":["Sarah K Hilton","Jesse D Bloom"],"journal":"Virus evolution","doi":"10.1093/ve/vey033","link":"https://academic.oup.com/ve/article/4/2/vey033/5163287","image":"/assets/papers/2018_hilton.jpg","keywords":["Phylogenetics"]},"headers":[],"relativePath":"papers/2018_hilton.md","filePath":"papers/2018_hilton.md"}'),a={name:"papers/2018_hilton.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Molecular phylogenetics is often used to estimate the time since the divergence of modern gene sequences. For highly diverged sequences, such phylogenetic techniques sometimes estimate surprisingly recent divergence times. In the case of viruses, independent evidence indicates that the estimates of deep divergence times from molecular phylogenetics are sometimes too recent. This discrepancy is caused in part by inadequate models of purifying selection leading to branch-length underestimation. Here we examine the effect on branch-length estimation of using models that incorporate experimental measurements of purifying selection. We find that models informed by experimentally measured site-specific amino-acid preferences estimate longer deep branches on phylogenies of influenza virus hemagglutinin. This lengthening of branches is due to more realistic stationary states of the models, and is mostly independent of the branch-length extension from modeling site-to-site variation in amino-acid substitution rate. The branch-length extension from experimentally informed site-specific models is similar to that achieved by other approaches that allow the stationary state to vary across sites. However, the improvements from all of these site-specific but time homogeneous and site independent models are limited by the fact that a protein’s amino-acid preferences gradually shift as it evolves. Overall, our work underscores the importance of modeling site-specific amino-acid preferences when estimating deep divergence times—but also shows the inherent limitations of approaches that fail to account for how these preferences shift over time.",-1),c=[o,r];function l(d,h,m,p,f,u){return s(),i("div",null,c)}const y=t(a,[["render",l]]);export{v as __pageData,y as default}; +import{_ as t,c as i,o as s,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const v=JSON.parse('{"title":"Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence","description":"","frontmatter":{"layout":"paper","title":"Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence","date":"2018-07-01","authors":["Sarah K Hilton","Jesse D Bloom"],"journal":"Virus evolution","doi":"10.1093/ve/vey033","link":"https://academic.oup.com/ve/article/4/2/vey033/5163287","image":"/assets/papers/2018_hilton.jpg","keywords":["Phylogenetics"]},"headers":[],"relativePath":"papers/2018_hilton.md","filePath":"papers/2018_hilton.md"}'),a={name:"papers/2018_hilton.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Molecular phylogenetics is often used to estimate the time since the divergence of modern gene sequences. For highly diverged sequences, such phylogenetic techniques sometimes estimate surprisingly recent divergence times. In the case of viruses, independent evidence indicates that the estimates of deep divergence times from molecular phylogenetics are sometimes too recent. This discrepancy is caused in part by inadequate models of purifying selection leading to branch-length underestimation. Here we examine the effect on branch-length estimation of using models that incorporate experimental measurements of purifying selection. We find that models informed by experimentally measured site-specific amino-acid preferences estimate longer deep branches on phylogenies of influenza virus hemagglutinin. This lengthening of branches is due to more realistic stationary states of the models, and is mostly independent of the branch-length extension from modeling site-to-site variation in amino-acid substitution rate. The branch-length extension from experimentally informed site-specific models is similar to that achieved by other approaches that allow the stationary state to vary across sites. However, the improvements from all of these site-specific but time homogeneous and site independent models are limited by the fact that a protein’s amino-acid preferences gradually shift as it evolves. Overall, our work underscores the importance of modeling site-specific amino-acid preferences when estimating deep divergence times—but also shows the inherent limitations of approaches that fail to account for how these preferences shift over time.",-1),c=[o,r];function l(d,h,m,p,f,u){return s(),i("div",null,c)}const y=t(a,[["render",l]]);export{v as __pageData,y as default}; diff --git a/assets/papers_2018_hilton.md.CFmlgqC8.lean.js b/assets/papers_2018_hilton.md.C49rLQnc.lean.js similarity index 97% rename from assets/papers_2018_hilton.md.CFmlgqC8.lean.js rename to assets/papers_2018_hilton.md.C49rLQnc.lean.js index 3bef7c7..2dec249 100644 --- a/assets/papers_2018_hilton.md.CFmlgqC8.lean.js +++ b/assets/papers_2018_hilton.md.C49rLQnc.lean.js @@ -1 +1 @@ -import{_ as t,c as i,o as s,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const v=JSON.parse('{"title":"Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence","description":"","frontmatter":{"layout":"paper","title":"Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence","date":"2018-07-01","authors":["Sarah K Hilton","Jesse D Bloom"],"journal":"Virus evolution","doi":"10.1093/ve/vey033","link":"https://academic.oup.com/ve/article/4/2/vey033/5163287","image":"/assets/papers/2018_hilton.jpg","keywords":["Phylogenetics"]},"headers":[],"relativePath":"papers/2018_hilton.md","filePath":"papers/2018_hilton.md"}'),a={name:"papers/2018_hilton.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Molecular phylogenetics is often used to estimate the time since the divergence of modern gene sequences. For highly diverged sequences, such phylogenetic techniques sometimes estimate surprisingly recent divergence times. In the case of viruses, independent evidence indicates that the estimates of deep divergence times from molecular phylogenetics are sometimes too recent. This discrepancy is caused in part by inadequate models of purifying selection leading to branch-length underestimation. Here we examine the effect on branch-length estimation of using models that incorporate experimental measurements of purifying selection. We find that models informed by experimentally measured site-specific amino-acid preferences estimate longer deep branches on phylogenies of influenza virus hemagglutinin. This lengthening of branches is due to more realistic stationary states of the models, and is mostly independent of the branch-length extension from modeling site-to-site variation in amino-acid substitution rate. The branch-length extension from experimentally informed site-specific models is similar to that achieved by other approaches that allow the stationary state to vary across sites. However, the improvements from all of these site-specific but time homogeneous and site independent models are limited by the fact that a protein’s amino-acid preferences gradually shift as it evolves. Overall, our work underscores the importance of modeling site-specific amino-acid preferences when estimating deep divergence times—but also shows the inherent limitations of approaches that fail to account for how these preferences shift over time.",-1),c=[o,r];function l(d,h,m,p,f,u){return s(),i("div",null,c)}const y=t(a,[["render",l]]);export{v as __pageData,y as default}; +import{_ as t,c as i,o as s,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const v=JSON.parse('{"title":"Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence","description":"","frontmatter":{"layout":"paper","title":"Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence","date":"2018-07-01","authors":["Sarah K Hilton","Jesse D Bloom"],"journal":"Virus evolution","doi":"10.1093/ve/vey033","link":"https://academic.oup.com/ve/article/4/2/vey033/5163287","image":"/assets/papers/2018_hilton.jpg","keywords":["Phylogenetics"]},"headers":[],"relativePath":"papers/2018_hilton.md","filePath":"papers/2018_hilton.md"}'),a={name:"papers/2018_hilton.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Molecular phylogenetics is often used to estimate the time since the divergence of modern gene sequences. For highly diverged sequences, such phylogenetic techniques sometimes estimate surprisingly recent divergence times. In the case of viruses, independent evidence indicates that the estimates of deep divergence times from molecular phylogenetics are sometimes too recent. This discrepancy is caused in part by inadequate models of purifying selection leading to branch-length underestimation. Here we examine the effect on branch-length estimation of using models that incorporate experimental measurements of purifying selection. We find that models informed by experimentally measured site-specific amino-acid preferences estimate longer deep branches on phylogenies of influenza virus hemagglutinin. This lengthening of branches is due to more realistic stationary states of the models, and is mostly independent of the branch-length extension from modeling site-to-site variation in amino-acid substitution rate. The branch-length extension from experimentally informed site-specific models is similar to that achieved by other approaches that allow the stationary state to vary across sites. However, the improvements from all of these site-specific but time homogeneous and site independent models are limited by the fact that a protein’s amino-acid preferences gradually shift as it evolves. Overall, our work underscores the importance of modeling site-specific amino-acid preferences when estimating deep divergence times—but also shows the inherent limitations of approaches that fail to account for how these preferences shift over time.",-1),c=[o,r];function l(d,h,m,p,f,u){return s(),i("div",null,c)}const y=t(a,[["render",l]]);export{v as __pageData,y as default}; diff --git a/assets/papers_2018_lee.md.CQEvBQHl.js b/assets/papers_2018_lee.md.BRV6Fb_g.js similarity index 97% rename from assets/papers_2018_lee.md.CQEvBQHl.js rename to assets/papers_2018_lee.md.BRV6Fb_g.js index 6b08391..b44a9e6 100644 --- a/assets/papers_2018_lee.md.CQEvBQHl.js +++ b/assets/papers_2018_lee.md.BRV6Fb_g.js @@ -1 +1 @@ -import{_ as a,c as t,o as n,b as e,d as s}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants","date":"2018-08-28","authors":["Juhye M Lee","John Huddleston","Michael B Doud","Kathryn A Hooper","Nicholas C Wu","Trevor Bedford","Jesse D Bloom"],"journal":"PNAS","doi":"10.1073/pnas.1806133115","link":"https://www.pnas.org/doi/abs/10.1073/pnas.1806133115","image":"/assets/papers/2018_lee.jpg","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2018_lee.md","filePath":"papers/2018_lee.md"}'),r={name:"papers/2018_lee.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Human influenza virus rapidly accumulates mutations in its major surface protein hemagglutinin (HA). The evolutionary success of influenza virus lineages depends on how these mutations affect HA’s functionality and antigenicity. Here we experimentally measure the effects on viral growth in cell culture of all single amino acid mutations to the HA from a recent human H3N2 influenza virus strain. We show that mutations that are measured to be more favorable for viral growth are enriched in evolutionarily successful H3N2 viral lineages relative to mutations that are measured to be less favorable for viral growth. Therefore, despite the well-known caveats about cell-culture measurements of viral fitness, such measurements can still be informative for understanding evolution in nature. We also compare our measurements for H3 HA to similar data previously generated for a distantly related H1 HA and find substantial differences in which amino acids are preferred at many sites. For instance, the H3 HA has less disparity in mutational tolerance between the head and stalk domains than the H1 HA. Overall, our work suggests that experimental measurements of mutational effects can be leveraged to help understand the evolutionary fates of viral lineages in nature—but only when the measurements are made on a viral strain similar to the ones being studied in nature.",-1),l=[i,o];function u(c,d,m,h,f,p){return n(),t("div",null,l)}const _=a(r,[["render",u]]);export{g as __pageData,_ as default}; +import{_ as a,c as t,o as n,b as e,d as s}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants","date":"2018-08-28","authors":["Juhye M Lee","John Huddleston","Michael B Doud","Kathryn A Hooper","Nicholas C Wu","Trevor Bedford","Jesse D Bloom"],"journal":"PNAS","doi":"10.1073/pnas.1806133115","link":"https://www.pnas.org/doi/abs/10.1073/pnas.1806133115","image":"/assets/papers/2018_lee.jpg","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2018_lee.md","filePath":"papers/2018_lee.md"}'),r={name:"papers/2018_lee.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Human influenza virus rapidly accumulates mutations in its major surface protein hemagglutinin (HA). The evolutionary success of influenza virus lineages depends on how these mutations affect HA’s functionality and antigenicity. Here we experimentally measure the effects on viral growth in cell culture of all single amino acid mutations to the HA from a recent human H3N2 influenza virus strain. We show that mutations that are measured to be more favorable for viral growth are enriched in evolutionarily successful H3N2 viral lineages relative to mutations that are measured to be less favorable for viral growth. Therefore, despite the well-known caveats about cell-culture measurements of viral fitness, such measurements can still be informative for understanding evolution in nature. We also compare our measurements for H3 HA to similar data previously generated for a distantly related H1 HA and find substantial differences in which amino acids are preferred at many sites. For instance, the H3 HA has less disparity in mutational tolerance between the head and stalk domains than the H1 HA. Overall, our work suggests that experimental measurements of mutational effects can be leveraged to help understand the evolutionary fates of viral lineages in nature—but only when the measurements are made on a viral strain similar to the ones being studied in nature.",-1),l=[i,o];function u(c,d,m,h,f,p){return n(),t("div",null,l)}const _=a(r,[["render",u]]);export{g as __pageData,_ as default}; diff --git a/assets/papers_2018_lee.md.CQEvBQHl.lean.js b/assets/papers_2018_lee.md.BRV6Fb_g.lean.js similarity index 97% rename from assets/papers_2018_lee.md.CQEvBQHl.lean.js rename to assets/papers_2018_lee.md.BRV6Fb_g.lean.js index 6b08391..b44a9e6 100644 --- a/assets/papers_2018_lee.md.CQEvBQHl.lean.js +++ b/assets/papers_2018_lee.md.BRV6Fb_g.lean.js @@ -1 +1 @@ -import{_ as a,c as t,o as n,b as e,d as s}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants","date":"2018-08-28","authors":["Juhye M Lee","John Huddleston","Michael B Doud","Kathryn A Hooper","Nicholas C Wu","Trevor Bedford","Jesse D Bloom"],"journal":"PNAS","doi":"10.1073/pnas.1806133115","link":"https://www.pnas.org/doi/abs/10.1073/pnas.1806133115","image":"/assets/papers/2018_lee.jpg","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2018_lee.md","filePath":"papers/2018_lee.md"}'),r={name:"papers/2018_lee.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Human influenza virus rapidly accumulates mutations in its major surface protein hemagglutinin (HA). The evolutionary success of influenza virus lineages depends on how these mutations affect HA’s functionality and antigenicity. Here we experimentally measure the effects on viral growth in cell culture of all single amino acid mutations to the HA from a recent human H3N2 influenza virus strain. We show that mutations that are measured to be more favorable for viral growth are enriched in evolutionarily successful H3N2 viral lineages relative to mutations that are measured to be less favorable for viral growth. Therefore, despite the well-known caveats about cell-culture measurements of viral fitness, such measurements can still be informative for understanding evolution in nature. We also compare our measurements for H3 HA to similar data previously generated for a distantly related H1 HA and find substantial differences in which amino acids are preferred at many sites. For instance, the H3 HA has less disparity in mutational tolerance between the head and stalk domains than the H1 HA. Overall, our work suggests that experimental measurements of mutational effects can be leveraged to help understand the evolutionary fates of viral lineages in nature—but only when the measurements are made on a viral strain similar to the ones being studied in nature.",-1),l=[i,o];function u(c,d,m,h,f,p){return n(),t("div",null,l)}const _=a(r,[["render",u]]);export{g as __pageData,_ as default}; +import{_ as a,c as t,o as n,b as e,d as s}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants","date":"2018-08-28","authors":["Juhye M Lee","John Huddleston","Michael B Doud","Kathryn A Hooper","Nicholas C Wu","Trevor Bedford","Jesse D Bloom"],"journal":"PNAS","doi":"10.1073/pnas.1806133115","link":"https://www.pnas.org/doi/abs/10.1073/pnas.1806133115","image":"/assets/papers/2018_lee.jpg","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2018_lee.md","filePath":"papers/2018_lee.md"}'),r={name:"papers/2018_lee.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Human influenza virus rapidly accumulates mutations in its major surface protein hemagglutinin (HA). The evolutionary success of influenza virus lineages depends on how these mutations affect HA’s functionality and antigenicity. Here we experimentally measure the effects on viral growth in cell culture of all single amino acid mutations to the HA from a recent human H3N2 influenza virus strain. We show that mutations that are measured to be more favorable for viral growth are enriched in evolutionarily successful H3N2 viral lineages relative to mutations that are measured to be less favorable for viral growth. Therefore, despite the well-known caveats about cell-culture measurements of viral fitness, such measurements can still be informative for understanding evolution in nature. We also compare our measurements for H3 HA to similar data previously generated for a distantly related H1 HA and find substantial differences in which amino acids are preferred at many sites. For instance, the H3 HA has less disparity in mutational tolerance between the head and stalk domains than the H1 HA. Overall, our work suggests that experimental measurements of mutational effects can be leveraged to help understand the evolutionary fates of viral lineages in nature—but only when the measurements are made on a viral strain similar to the ones being studied in nature.",-1),l=[i,o];function u(c,d,m,h,f,p){return n(),t("div",null,l)}const _=a(r,[["render",u]]);export{g as __pageData,_ as default}; diff --git a/assets/papers_2018_russell.md.xaiArK1b.js b/assets/papers_2018_russell.md.wgx_bish.js similarity index 96% rename from assets/papers_2018_russell.md.xaiArK1b.js rename to assets/papers_2018_russell.md.wgx_bish.js index eaa8aaf..31f12ea 100644 --- a/assets/papers_2018_russell.md.xaiArK1b.js +++ b/assets/papers_2018_russell.md.wgx_bish.js @@ -1 +1 @@ -import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Extreme heterogeneity of influenza virus infection in single cells","description":"","frontmatter":{"layout":"paper","title":"Extreme heterogeneity of influenza virus infection in single cells","date":"2018-02-16","authors":["Alistair B Russell","Cole Trapnell","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.32303","link":"https://elifesciences.org/articles/32303","image":"/assets/papers/2018_russell.jpg","keywords":["Influenza","Single-cell sequencing"]},"headers":[],"relativePath":"papers/2018_russell.md","filePath":"papers/2018_russell.md"}'),l={name:"papers/2018_russell.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Viral infection can dramatically alter a cell’s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in the productivity of viral transcription – viral transcripts comprise less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, but this gene absence only partially explains variation in viral transcriptional load. Despite variation in viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells.",-1),o=[n,r];function c(u,f,p,d,m,h){return s(),a("div",null,o)}const g=t(l,[["render",c]]);export{_ as __pageData,g as default}; +import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Extreme heterogeneity of influenza virus infection in single cells","description":"","frontmatter":{"layout":"paper","title":"Extreme heterogeneity of influenza virus infection in single cells","date":"2018-02-16","authors":["Alistair B Russell","Cole Trapnell","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.32303","link":"https://elifesciences.org/articles/32303","image":"/assets/papers/2018_russell.jpg","keywords":["Influenza","Single-cell sequencing"]},"headers":[],"relativePath":"papers/2018_russell.md","filePath":"papers/2018_russell.md"}'),l={name:"papers/2018_russell.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Viral infection can dramatically alter a cell’s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in the productivity of viral transcription – viral transcripts comprise less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, but this gene absence only partially explains variation in viral transcriptional load. Despite variation in viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells.",-1),o=[n,r];function c(u,f,p,d,m,h){return s(),a("div",null,o)}const g=t(l,[["render",c]]);export{_ as __pageData,g as default}; diff --git a/assets/papers_2018_russell.md.xaiArK1b.lean.js b/assets/papers_2018_russell.md.wgx_bish.lean.js similarity index 96% rename from assets/papers_2018_russell.md.xaiArK1b.lean.js rename to assets/papers_2018_russell.md.wgx_bish.lean.js index eaa8aaf..31f12ea 100644 --- a/assets/papers_2018_russell.md.xaiArK1b.lean.js +++ b/assets/papers_2018_russell.md.wgx_bish.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Extreme heterogeneity of influenza virus infection in single cells","description":"","frontmatter":{"layout":"paper","title":"Extreme heterogeneity of influenza virus infection in single cells","date":"2018-02-16","authors":["Alistair B Russell","Cole Trapnell","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.32303","link":"https://elifesciences.org/articles/32303","image":"/assets/papers/2018_russell.jpg","keywords":["Influenza","Single-cell sequencing"]},"headers":[],"relativePath":"papers/2018_russell.md","filePath":"papers/2018_russell.md"}'),l={name:"papers/2018_russell.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Viral infection can dramatically alter a cell’s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in the productivity of viral transcription – viral transcripts comprise less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, but this gene absence only partially explains variation in viral transcriptional load. Despite variation in viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells.",-1),o=[n,r];function c(u,f,p,d,m,h){return s(),a("div",null,o)}const g=t(l,[["render",c]]);export{_ as __pageData,g as default}; +import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Extreme heterogeneity of influenza virus infection in single cells","description":"","frontmatter":{"layout":"paper","title":"Extreme heterogeneity of influenza virus infection in single cells","date":"2018-02-16","authors":["Alistair B Russell","Cole Trapnell","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.32303","link":"https://elifesciences.org/articles/32303","image":"/assets/papers/2018_russell.jpg","keywords":["Influenza","Single-cell sequencing"]},"headers":[],"relativePath":"papers/2018_russell.md","filePath":"papers/2018_russell.md"}'),l={name:"papers/2018_russell.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Viral infection can dramatically alter a cell’s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in the productivity of viral transcription – viral transcripts comprise less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, but this gene absence only partially explains variation in viral transcriptional load. Despite variation in viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells.",-1),o=[n,r];function c(u,f,p,d,m,h){return s(),a("div",null,o)}const g=t(l,[["render",c]]);export{_ as __pageData,g as default}; diff --git a/assets/papers_2018_xue_a.md.CcjMEJe5.js b/assets/papers_2018_xue_a.md.CEdqDxk1.js similarity index 96% rename from assets/papers_2018_xue_a.md.CcjMEJe5.js rename to assets/papers_2018_xue_a.md.CEdqDxk1.js index 9bc2013..dd3651e 100644 --- a/assets/papers_2018_xue_a.md.CcjMEJe5.js +++ b/assets/papers_2018_xue_a.md.CEdqDxk1.js @@ -1 +1 @@ -import{_ as t,c as i,o as n,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const m=JSON.parse('{"title":"Within-host evolution of human influenza virus","description":"","frontmatter":{"layout":"paper","title":"Within-host evolution of human influenza virus","date":"2018-09-01","authors":["Katherine S Xue","Louise H Moncla","Trevor Bedford","Jesse D Bloom"],"journal":"Trends in Microbiology","doi":"10.1016/j.tim.2018.02.007","link":"https://www.cell.com/trends/microbiology/fulltext/S0966-842X(18)30043-X","image":"/assets/papers/2018_xue_a.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2018_xue_a.md","filePath":"papers/2018_xue_a.md"}'),a={name:"papers/2018_xue_a.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The rapid global evolution of influenza virus begins with mutations that arise de novo in individual infections, but little is known about how evolution occurs within hosts. We review recent progress in understanding how and why influenza viruses evolve within human hosts. Advances in deep sequencing make it possible to measure within-host genetic diversity in both acute and chronic influenza infections. Factors like antigenic selection, antiviral treatment, tissue specificity, spatial structure, and multiplicity of infection may affect how influenza viruses evolve within human hosts. Studies of within-host evolution can contribute to our understanding of the evolutionary and epidemiological factors that shape influenza virus's global evolution.",-1),l=[s,r];function u(c,h,d,p,f,_){return n(),i("div",null,l)}const b=t(a,[["render",u]]);export{m as __pageData,b as default}; +import{_ as t,c as i,o as n,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const m=JSON.parse('{"title":"Within-host evolution of human influenza virus","description":"","frontmatter":{"layout":"paper","title":"Within-host evolution of human influenza virus","date":"2018-09-01","authors":["Katherine S Xue","Louise H Moncla","Trevor Bedford","Jesse D Bloom"],"journal":"Trends in Microbiology","doi":"10.1016/j.tim.2018.02.007","link":"https://www.cell.com/trends/microbiology/fulltext/S0966-842X(18)30043-X","image":"/assets/papers/2018_xue_a.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2018_xue_a.md","filePath":"papers/2018_xue_a.md"}'),a={name:"papers/2018_xue_a.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The rapid global evolution of influenza virus begins with mutations that arise de novo in individual infections, but little is known about how evolution occurs within hosts. We review recent progress in understanding how and why influenza viruses evolve within human hosts. Advances in deep sequencing make it possible to measure within-host genetic diversity in both acute and chronic influenza infections. Factors like antigenic selection, antiviral treatment, tissue specificity, spatial structure, and multiplicity of infection may affect how influenza viruses evolve within human hosts. Studies of within-host evolution can contribute to our understanding of the evolutionary and epidemiological factors that shape influenza virus's global evolution.",-1),l=[s,r];function u(c,h,d,p,f,_){return n(),i("div",null,l)}const b=t(a,[["render",u]]);export{m as __pageData,b as default}; diff --git a/assets/papers_2018_xue_a.md.CcjMEJe5.lean.js b/assets/papers_2018_xue_a.md.CEdqDxk1.lean.js similarity index 96% rename from assets/papers_2018_xue_a.md.CcjMEJe5.lean.js rename to assets/papers_2018_xue_a.md.CEdqDxk1.lean.js index 9bc2013..dd3651e 100644 --- a/assets/papers_2018_xue_a.md.CcjMEJe5.lean.js +++ b/assets/papers_2018_xue_a.md.CEdqDxk1.lean.js @@ -1 +1 @@ -import{_ as t,c as i,o as n,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const m=JSON.parse('{"title":"Within-host evolution of human influenza virus","description":"","frontmatter":{"layout":"paper","title":"Within-host evolution of human influenza virus","date":"2018-09-01","authors":["Katherine S Xue","Louise H Moncla","Trevor Bedford","Jesse D Bloom"],"journal":"Trends in Microbiology","doi":"10.1016/j.tim.2018.02.007","link":"https://www.cell.com/trends/microbiology/fulltext/S0966-842X(18)30043-X","image":"/assets/papers/2018_xue_a.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2018_xue_a.md","filePath":"papers/2018_xue_a.md"}'),a={name:"papers/2018_xue_a.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The rapid global evolution of influenza virus begins with mutations that arise de novo in individual infections, but little is known about how evolution occurs within hosts. We review recent progress in understanding how and why influenza viruses evolve within human hosts. Advances in deep sequencing make it possible to measure within-host genetic diversity in both acute and chronic influenza infections. Factors like antigenic selection, antiviral treatment, tissue specificity, spatial structure, and multiplicity of infection may affect how influenza viruses evolve within human hosts. Studies of within-host evolution can contribute to our understanding of the evolutionary and epidemiological factors that shape influenza virus's global evolution.",-1),l=[s,r];function u(c,h,d,p,f,_){return n(),i("div",null,l)}const b=t(a,[["render",u]]);export{m as __pageData,b as default}; +import{_ as t,c as i,o as n,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const m=JSON.parse('{"title":"Within-host evolution of human influenza virus","description":"","frontmatter":{"layout":"paper","title":"Within-host evolution of human influenza virus","date":"2018-09-01","authors":["Katherine S Xue","Louise H Moncla","Trevor Bedford","Jesse D Bloom"],"journal":"Trends in Microbiology","doi":"10.1016/j.tim.2018.02.007","link":"https://www.cell.com/trends/microbiology/fulltext/S0966-842X(18)30043-X","image":"/assets/papers/2018_xue_a.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2018_xue_a.md","filePath":"papers/2018_xue_a.md"}'),a={name:"papers/2018_xue_a.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The rapid global evolution of influenza virus begins with mutations that arise de novo in individual infections, but little is known about how evolution occurs within hosts. We review recent progress in understanding how and why influenza viruses evolve within human hosts. Advances in deep sequencing make it possible to measure within-host genetic diversity in both acute and chronic influenza infections. Factors like antigenic selection, antiviral treatment, tissue specificity, spatial structure, and multiplicity of infection may affect how influenza viruses evolve within human hosts. Studies of within-host evolution can contribute to our understanding of the evolutionary and epidemiological factors that shape influenza virus's global evolution.",-1),l=[s,r];function u(c,h,d,p,f,_){return n(),i("div",null,l)}const b=t(a,[["render",u]]);export{m as __pageData,b as default}; diff --git a/assets/papers_2018_xue_b.md.BtkdwrPc.js b/assets/papers_2018_xue_b.md.KLBeer-G.js similarity index 97% rename from assets/papers_2018_xue_b.md.BtkdwrPc.js rename to assets/papers_2018_xue_b.md.KLBeer-G.js index 155e670..8420f56 100644 --- a/assets/papers_2018_xue_b.md.BtkdwrPc.js +++ b/assets/papers_2018_xue_b.md.KLBeer-G.js @@ -1 +1 @@ -import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples","description":"","frontmatter":{"layout":"paper","title":"Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples","date":"2018-02-28","authors":["Katherine S Xue","Alexander L Greninger","Ailyn Pérez-Osorio","Jesse D Bloom"],"journal":"MSphere","doi":"10.1128/mspheredirect.00552-17","link":"https://journals.asm.org/doi/full/10.1128/mspheredirect.00552-17","image":"/assets/papers/2018_xue_b.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2018_xue_b.md","filePath":"papers/2018_xue_b.md"}'),r={name:"papers/2018_xue_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"The high mutation rates of RNA viruses lead to rapid genetic diversification, which can enable cooperative interactions between variants in a viral population. We previously described two distinct variants of H3N2 influenza virus that cooperate in cell culture. These variants differ by a single mutation, D151G, in the neuraminidase protein. The D151G mutation reaches a stable frequency of about 50% when virus is passaged in cell culture. However, it is unclear whether selection for the cooperative benefits of D151G is a cell culture phenomenon or whether the mutation is also sometimes present at appreciable frequency in virus populations sampled directly from infected humans. Prior work has not detected D151G in unpassaged clinical samples, but those studies have used methods like Sanger sequencing and pyrosequencing, which are relatively insensitive to low-frequency variation. We identified nine samples of human H3N2 influenza virus collected between 2013 and 2015 in which Sanger sequencing had detected a high frequency of the D151G mutation following one to three passages in cell culture. We deep sequenced the unpassaged clinical samples to identify low-frequency viral variants. The frequency of D151G did not exceed the frequency of library preparation and sequencing errors in any of the sequenced samples. We conclude that passage in cell culture is primarily responsible for the frequent observations of D151G in recent H3N2 influenza virus strains.",-1),l=[s,o];function c(u,d,p,h,f,m){return i(),t("div",null,l)}const b=a(r,[["render",c]]);export{_ as __pageData,b as default}; +import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples","description":"","frontmatter":{"layout":"paper","title":"Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples","date":"2018-02-28","authors":["Katherine S Xue","Alexander L Greninger","Ailyn Pérez-Osorio","Jesse D Bloom"],"journal":"MSphere","doi":"10.1128/mspheredirect.00552-17","link":"https://journals.asm.org/doi/full/10.1128/mspheredirect.00552-17","image":"/assets/papers/2018_xue_b.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2018_xue_b.md","filePath":"papers/2018_xue_b.md"}'),r={name:"papers/2018_xue_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"The high mutation rates of RNA viruses lead to rapid genetic diversification, which can enable cooperative interactions between variants in a viral population. We previously described two distinct variants of H3N2 influenza virus that cooperate in cell culture. These variants differ by a single mutation, D151G, in the neuraminidase protein. The D151G mutation reaches a stable frequency of about 50% when virus is passaged in cell culture. However, it is unclear whether selection for the cooperative benefits of D151G is a cell culture phenomenon or whether the mutation is also sometimes present at appreciable frequency in virus populations sampled directly from infected humans. Prior work has not detected D151G in unpassaged clinical samples, but those studies have used methods like Sanger sequencing and pyrosequencing, which are relatively insensitive to low-frequency variation. We identified nine samples of human H3N2 influenza virus collected between 2013 and 2015 in which Sanger sequencing had detected a high frequency of the D151G mutation following one to three passages in cell culture. We deep sequenced the unpassaged clinical samples to identify low-frequency viral variants. The frequency of D151G did not exceed the frequency of library preparation and sequencing errors in any of the sequenced samples. We conclude that passage in cell culture is primarily responsible for the frequent observations of D151G in recent H3N2 influenza virus strains.",-1),l=[s,o];function c(u,d,p,h,f,m){return i(),t("div",null,l)}const b=a(r,[["render",c]]);export{_ as __pageData,b as default}; diff --git a/assets/papers_2018_xue_b.md.BtkdwrPc.lean.js b/assets/papers_2018_xue_b.md.KLBeer-G.lean.js similarity index 97% rename from assets/papers_2018_xue_b.md.BtkdwrPc.lean.js rename to assets/papers_2018_xue_b.md.KLBeer-G.lean.js index 155e670..8420f56 100644 --- a/assets/papers_2018_xue_b.md.BtkdwrPc.lean.js +++ b/assets/papers_2018_xue_b.md.KLBeer-G.lean.js @@ -1 +1 @@ -import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples","description":"","frontmatter":{"layout":"paper","title":"Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples","date":"2018-02-28","authors":["Katherine S Xue","Alexander L Greninger","Ailyn Pérez-Osorio","Jesse D Bloom"],"journal":"MSphere","doi":"10.1128/mspheredirect.00552-17","link":"https://journals.asm.org/doi/full/10.1128/mspheredirect.00552-17","image":"/assets/papers/2018_xue_b.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2018_xue_b.md","filePath":"papers/2018_xue_b.md"}'),r={name:"papers/2018_xue_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"The high mutation rates of RNA viruses lead to rapid genetic diversification, which can enable cooperative interactions between variants in a viral population. We previously described two distinct variants of H3N2 influenza virus that cooperate in cell culture. These variants differ by a single mutation, D151G, in the neuraminidase protein. The D151G mutation reaches a stable frequency of about 50% when virus is passaged in cell culture. However, it is unclear whether selection for the cooperative benefits of D151G is a cell culture phenomenon or whether the mutation is also sometimes present at appreciable frequency in virus populations sampled directly from infected humans. Prior work has not detected D151G in unpassaged clinical samples, but those studies have used methods like Sanger sequencing and pyrosequencing, which are relatively insensitive to low-frequency variation. We identified nine samples of human H3N2 influenza virus collected between 2013 and 2015 in which Sanger sequencing had detected a high frequency of the D151G mutation following one to three passages in cell culture. We deep sequenced the unpassaged clinical samples to identify low-frequency viral variants. The frequency of D151G did not exceed the frequency of library preparation and sequencing errors in any of the sequenced samples. We conclude that passage in cell culture is primarily responsible for the frequent observations of D151G in recent H3N2 influenza virus strains.",-1),l=[s,o];function c(u,d,p,h,f,m){return i(),t("div",null,l)}const b=a(r,[["render",c]]);export{_ as __pageData,b as default}; +import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples","description":"","frontmatter":{"layout":"paper","title":"Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples","date":"2018-02-28","authors":["Katherine S Xue","Alexander L Greninger","Ailyn Pérez-Osorio","Jesse D Bloom"],"journal":"MSphere","doi":"10.1128/mspheredirect.00552-17","link":"https://journals.asm.org/doi/full/10.1128/mspheredirect.00552-17","image":"/assets/papers/2018_xue_b.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2018_xue_b.md","filePath":"papers/2018_xue_b.md"}'),r={name:"papers/2018_xue_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"The high mutation rates of RNA viruses lead to rapid genetic diversification, which can enable cooperative interactions between variants in a viral population. We previously described two distinct variants of H3N2 influenza virus that cooperate in cell culture. These variants differ by a single mutation, D151G, in the neuraminidase protein. The D151G mutation reaches a stable frequency of about 50% when virus is passaged in cell culture. However, it is unclear whether selection for the cooperative benefits of D151G is a cell culture phenomenon or whether the mutation is also sometimes present at appreciable frequency in virus populations sampled directly from infected humans. Prior work has not detected D151G in unpassaged clinical samples, but those studies have used methods like Sanger sequencing and pyrosequencing, which are relatively insensitive to low-frequency variation. We identified nine samples of human H3N2 influenza virus collected between 2013 and 2015 in which Sanger sequencing had detected a high frequency of the D151G mutation following one to three passages in cell culture. We deep sequenced the unpassaged clinical samples to identify low-frequency viral variants. The frequency of D151G did not exceed the frequency of library preparation and sequencing errors in any of the sequenced samples. We conclude that passage in cell culture is primarily responsible for the frequent observations of D151G in recent H3N2 influenza virus strains.",-1),l=[s,o];function c(u,d,p,h,f,m){return i(),t("div",null,l)}const b=a(r,[["render",c]]);export{_ as __pageData,b as default}; diff --git a/assets/papers_2019_crawford.md.SIB_xdRS.js b/assets/papers_2019_crawford.md.s7R-zLVQ.js similarity index 96% rename from assets/papers_2019_crawford.md.SIB_xdRS.js rename to assets/papers_2019_crawford.md.s7R-zLVQ.js index dee636e..f96e171 100644 --- a/assets/papers_2019_crawford.md.SIB_xdRS.js +++ b/assets/papers_2019_crawford.md.s7R-zLVQ.js @@ -1 +1 @@ -import{_ as a,c as s,o as t,b as e,d as r}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"alignparse: A Python package for parsing complex features from high-throughput long-read sequencing","description":"","frontmatter":{"layout":"paper","title":"alignparse: A Python package for parsing complex features from high-throughput long-read sequencing","date":"2019-01-23","authors":["Katharine HD Crawford","Jesse D Bloom"],"journal":"JOSS","doi":"10.21105/joss.01915","link":"https://doi.org/10.21105%2Fjoss.01915","image":"/assets/papers/2019_crawford.png","keywords":["Software tools"]},"headers":[],"relativePath":"papers/2019_crawford.md","filePath":"papers/2019_crawford.md"}'),n={name:"papers/2019_crawford.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"Advances in sequencing technology have made it possible to generate large numbers of long, high-accuracy sequencing reads. For instance, the new PacBio Sequel platform can generate hundreds of thousands of high-quality circular consensus sequences in a single run (Hebert et al., 2018; Rhoads & Au, 2015). Good programs exist for aligning these reads for genome assembly (Chaisson & Tesler, 2012; Li, 2018). However, these long reads can also be used for other purposes, such as sequencing PCR amplicons that contain various features of interest. For instance, PacBio circular consensus sequences have been used to identify the mutations in influenza viruses in single cells (Russell et al, 2019), or to link barcodes to gene mutants in deep mutational scanning (Matreyek et al., 2018). For such applications, the alignment of the sequences to the targets may be fairly trivial, but it is not trivial to then parse specific features of interest (such as mutations, unique molecular identifiers, cell barcodes, and flanking sequences) from these alignments.",-1),c=[o,i];function l(u,d,h,p,f,g){return t(),s("div",null,c)}const b=a(n,[["render",l]]);export{_ as __pageData,b as default}; +import{_ as a,c as s,o as t,b as e,d as r}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"alignparse: A Python package for parsing complex features from high-throughput long-read sequencing","description":"","frontmatter":{"layout":"paper","title":"alignparse: A Python package for parsing complex features from high-throughput long-read sequencing","date":"2019-01-23","authors":["Katharine HD Crawford","Jesse D Bloom"],"journal":"JOSS","doi":"10.21105/joss.01915","link":"https://doi.org/10.21105%2Fjoss.01915","image":"/assets/papers/2019_crawford.png","keywords":["Software tools"]},"headers":[],"relativePath":"papers/2019_crawford.md","filePath":"papers/2019_crawford.md"}'),n={name:"papers/2019_crawford.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"Advances in sequencing technology have made it possible to generate large numbers of long, high-accuracy sequencing reads. For instance, the new PacBio Sequel platform can generate hundreds of thousands of high-quality circular consensus sequences in a single run (Hebert et al., 2018; Rhoads & Au, 2015). Good programs exist for aligning these reads for genome assembly (Chaisson & Tesler, 2012; Li, 2018). However, these long reads can also be used for other purposes, such as sequencing PCR amplicons that contain various features of interest. For instance, PacBio circular consensus sequences have been used to identify the mutations in influenza viruses in single cells (Russell et al, 2019), or to link barcodes to gene mutants in deep mutational scanning (Matreyek et al., 2018). For such applications, the alignment of the sequences to the targets may be fairly trivial, but it is not trivial to then parse specific features of interest (such as mutations, unique molecular identifiers, cell barcodes, and flanking sequences) from these alignments.",-1),c=[o,i];function l(u,d,h,p,f,g){return t(),s("div",null,c)}const b=a(n,[["render",l]]);export{_ as __pageData,b as default}; diff --git a/assets/papers_2019_crawford.md.SIB_xdRS.lean.js b/assets/papers_2019_crawford.md.s7R-zLVQ.lean.js similarity index 96% rename from assets/papers_2019_crawford.md.SIB_xdRS.lean.js rename to assets/papers_2019_crawford.md.s7R-zLVQ.lean.js index dee636e..f96e171 100644 --- a/assets/papers_2019_crawford.md.SIB_xdRS.lean.js +++ b/assets/papers_2019_crawford.md.s7R-zLVQ.lean.js @@ -1 +1 @@ -import{_ as a,c as s,o as t,b as e,d as r}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"alignparse: A Python package for parsing complex features from high-throughput long-read sequencing","description":"","frontmatter":{"layout":"paper","title":"alignparse: A Python package for parsing complex features from high-throughput long-read sequencing","date":"2019-01-23","authors":["Katharine HD Crawford","Jesse D Bloom"],"journal":"JOSS","doi":"10.21105/joss.01915","link":"https://doi.org/10.21105%2Fjoss.01915","image":"/assets/papers/2019_crawford.png","keywords":["Software tools"]},"headers":[],"relativePath":"papers/2019_crawford.md","filePath":"papers/2019_crawford.md"}'),n={name:"papers/2019_crawford.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"Advances in sequencing technology have made it possible to generate large numbers of long, high-accuracy sequencing reads. For instance, the new PacBio Sequel platform can generate hundreds of thousands of high-quality circular consensus sequences in a single run (Hebert et al., 2018; Rhoads & Au, 2015). Good programs exist for aligning these reads for genome assembly (Chaisson & Tesler, 2012; Li, 2018). However, these long reads can also be used for other purposes, such as sequencing PCR amplicons that contain various features of interest. For instance, PacBio circular consensus sequences have been used to identify the mutations in influenza viruses in single cells (Russell et al, 2019), or to link barcodes to gene mutants in deep mutational scanning (Matreyek et al., 2018). For such applications, the alignment of the sequences to the targets may be fairly trivial, but it is not trivial to then parse specific features of interest (such as mutations, unique molecular identifiers, cell barcodes, and flanking sequences) from these alignments.",-1),c=[o,i];function l(u,d,h,p,f,g){return t(),s("div",null,c)}const b=a(n,[["render",l]]);export{_ as __pageData,b as default}; +import{_ as a,c as s,o as t,b as e,d as r}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"alignparse: A Python package for parsing complex features from high-throughput long-read sequencing","description":"","frontmatter":{"layout":"paper","title":"alignparse: A Python package for parsing complex features from high-throughput long-read sequencing","date":"2019-01-23","authors":["Katharine HD Crawford","Jesse D Bloom"],"journal":"JOSS","doi":"10.21105/joss.01915","link":"https://doi.org/10.21105%2Fjoss.01915","image":"/assets/papers/2019_crawford.png","keywords":["Software tools"]},"headers":[],"relativePath":"papers/2019_crawford.md","filePath":"papers/2019_crawford.md"}'),n={name:"papers/2019_crawford.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"Advances in sequencing technology have made it possible to generate large numbers of long, high-accuracy sequencing reads. For instance, the new PacBio Sequel platform can generate hundreds of thousands of high-quality circular consensus sequences in a single run (Hebert et al., 2018; Rhoads & Au, 2015). Good programs exist for aligning these reads for genome assembly (Chaisson & Tesler, 2012; Li, 2018). However, these long reads can also be used for other purposes, such as sequencing PCR amplicons that contain various features of interest. For instance, PacBio circular consensus sequences have been used to identify the mutations in influenza viruses in single cells (Russell et al, 2019), or to link barcodes to gene mutants in deep mutational scanning (Matreyek et al., 2018). For such applications, the alignment of the sequences to the targets may be fairly trivial, but it is not trivial to then parse specific features of interest (such as mutations, unique molecular identifiers, cell barcodes, and flanking sequences) from these alignments.",-1),c=[o,i];function l(u,d,h,p,f,g){return t(),s("div",null,c)}const b=a(n,[["render",l]]);export{_ as __pageData,b as default}; diff --git a/assets/papers_2019_dingens_a.md.BgRe_r1V.js b/assets/papers_2019_dingens_a.md.IrHjZDnk.js similarity index 97% rename from assets/papers_2019_dingens_a.md.BgRe_r1V.js rename to assets/papers_2019_dingens_a.md.IrHjZDnk.js index edc54fe..73e5f91 100644 --- a/assets/papers_2019_dingens_a.md.BgRe_r1V.js +++ b/assets/papers_2019_dingens_a.md.IrHjZDnk.js @@ -1 +1 @@ -import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.BqSDeblO.js";const v=JSON.parse('{"title":"Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide","description":"","frontmatter":{"layout":"paper","title":"Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide","date":"2019-05-15","authors":["Adam S Dingens","Dana Arenz","Julie Overbaugh","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v11050439","link":"https://www.mdpi.com/1999-4915/11/5/439","image":"/assets/papers/2019_dingens_a.jpg","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2019_dingens_a.md","filePath":"papers/2019_dingens_a.md"}'),s={name:"papers/2019_dingens_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Identifying drug resistance mutations is important for the clinical use of antivirals and can help define both a drug’s mechanism of action and the mechanistic basis of resistance. Resistance mutations are often identified one-at-a-time by studying viral evolution within treated patients or during viral growth in the presence of a drug in cell culture. Such approaches have previously mapped resistance to enfuvirtide, the only clinically approved HIV-1 fusion inhibitor, to enfuvirtide’s binding site in the N-terminal heptad repeat (NHR) of the Envelope (Env) transmembrane domain as well as a limited number of allosteric sites. Here, we sought to better delineate the genotypic determinants of resistance throughout Env. We used deep mutational scanning to quantify the effect of all single-amino-acid mutations to the subtype A BG505 Env on resistance to enfuvirtide. We identified both previously characterized and numerous novel resistance mutations in the NHR. Additional resistance mutations clustered in other regions of Env conformational intermediates, suggesting they may act during different fusion steps by altering fusion kinetics and/or exposure of the enfuvirtide binding site. This complete map of resistance sheds light on the diverse mechanisms of enfuvirtide resistance and highlights the utility of using deep mutational scanning to comprehensively map potential drug resistance mutations.",-1),d=[o,r];function l(c,u,h,p,f,m){return n(),i("div",null,d)}const _=t(s,[["render",l]]);export{v as __pageData,_ as default}; +import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.D4bY2S_W.js";const v=JSON.parse('{"title":"Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide","description":"","frontmatter":{"layout":"paper","title":"Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide","date":"2019-05-15","authors":["Adam S Dingens","Dana Arenz","Julie Overbaugh","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v11050439","link":"https://www.mdpi.com/1999-4915/11/5/439","image":"/assets/papers/2019_dingens_a.jpg","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2019_dingens_a.md","filePath":"papers/2019_dingens_a.md"}'),s={name:"papers/2019_dingens_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Identifying drug resistance mutations is important for the clinical use of antivirals and can help define both a drug’s mechanism of action and the mechanistic basis of resistance. Resistance mutations are often identified one-at-a-time by studying viral evolution within treated patients or during viral growth in the presence of a drug in cell culture. Such approaches have previously mapped resistance to enfuvirtide, the only clinically approved HIV-1 fusion inhibitor, to enfuvirtide’s binding site in the N-terminal heptad repeat (NHR) of the Envelope (Env) transmembrane domain as well as a limited number of allosteric sites. Here, we sought to better delineate the genotypic determinants of resistance throughout Env. We used deep mutational scanning to quantify the effect of all single-amino-acid mutations to the subtype A BG505 Env on resistance to enfuvirtide. We identified both previously characterized and numerous novel resistance mutations in the NHR. Additional resistance mutations clustered in other regions of Env conformational intermediates, suggesting they may act during different fusion steps by altering fusion kinetics and/or exposure of the enfuvirtide binding site. This complete map of resistance sheds light on the diverse mechanisms of enfuvirtide resistance and highlights the utility of using deep mutational scanning to comprehensively map potential drug resistance mutations.",-1),d=[o,r];function l(c,u,h,p,f,m){return n(),i("div",null,d)}const _=t(s,[["render",l]]);export{v as __pageData,_ as default}; diff --git a/assets/papers_2019_dingens_a.md.BgRe_r1V.lean.js b/assets/papers_2019_dingens_a.md.IrHjZDnk.lean.js similarity index 97% rename from assets/papers_2019_dingens_a.md.BgRe_r1V.lean.js rename to assets/papers_2019_dingens_a.md.IrHjZDnk.lean.js index edc54fe..73e5f91 100644 --- a/assets/papers_2019_dingens_a.md.BgRe_r1V.lean.js +++ b/assets/papers_2019_dingens_a.md.IrHjZDnk.lean.js @@ -1 +1 @@ -import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.BqSDeblO.js";const v=JSON.parse('{"title":"Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide","description":"","frontmatter":{"layout":"paper","title":"Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide","date":"2019-05-15","authors":["Adam S Dingens","Dana Arenz","Julie Overbaugh","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v11050439","link":"https://www.mdpi.com/1999-4915/11/5/439","image":"/assets/papers/2019_dingens_a.jpg","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2019_dingens_a.md","filePath":"papers/2019_dingens_a.md"}'),s={name:"papers/2019_dingens_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Identifying drug resistance mutations is important for the clinical use of antivirals and can help define both a drug’s mechanism of action and the mechanistic basis of resistance. Resistance mutations are often identified one-at-a-time by studying viral evolution within treated patients or during viral growth in the presence of a drug in cell culture. Such approaches have previously mapped resistance to enfuvirtide, the only clinically approved HIV-1 fusion inhibitor, to enfuvirtide’s binding site in the N-terminal heptad repeat (NHR) of the Envelope (Env) transmembrane domain as well as a limited number of allosteric sites. Here, we sought to better delineate the genotypic determinants of resistance throughout Env. We used deep mutational scanning to quantify the effect of all single-amino-acid mutations to the subtype A BG505 Env on resistance to enfuvirtide. We identified both previously characterized and numerous novel resistance mutations in the NHR. Additional resistance mutations clustered in other regions of Env conformational intermediates, suggesting they may act during different fusion steps by altering fusion kinetics and/or exposure of the enfuvirtide binding site. This complete map of resistance sheds light on the diverse mechanisms of enfuvirtide resistance and highlights the utility of using deep mutational scanning to comprehensively map potential drug resistance mutations.",-1),d=[o,r];function l(c,u,h,p,f,m){return n(),i("div",null,d)}const _=t(s,[["render",l]]);export{v as __pageData,_ as default}; +import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.D4bY2S_W.js";const v=JSON.parse('{"title":"Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide","description":"","frontmatter":{"layout":"paper","title":"Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide","date":"2019-05-15","authors":["Adam S Dingens","Dana Arenz","Julie Overbaugh","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v11050439","link":"https://www.mdpi.com/1999-4915/11/5/439","image":"/assets/papers/2019_dingens_a.jpg","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2019_dingens_a.md","filePath":"papers/2019_dingens_a.md"}'),s={name:"papers/2019_dingens_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Identifying drug resistance mutations is important for the clinical use of antivirals and can help define both a drug’s mechanism of action and the mechanistic basis of resistance. Resistance mutations are often identified one-at-a-time by studying viral evolution within treated patients or during viral growth in the presence of a drug in cell culture. Such approaches have previously mapped resistance to enfuvirtide, the only clinically approved HIV-1 fusion inhibitor, to enfuvirtide’s binding site in the N-terminal heptad repeat (NHR) of the Envelope (Env) transmembrane domain as well as a limited number of allosteric sites. Here, we sought to better delineate the genotypic determinants of resistance throughout Env. We used deep mutational scanning to quantify the effect of all single-amino-acid mutations to the subtype A BG505 Env on resistance to enfuvirtide. We identified both previously characterized and numerous novel resistance mutations in the NHR. Additional resistance mutations clustered in other regions of Env conformational intermediates, suggesting they may act during different fusion steps by altering fusion kinetics and/or exposure of the enfuvirtide binding site. This complete map of resistance sheds light on the diverse mechanisms of enfuvirtide resistance and highlights the utility of using deep mutational scanning to comprehensively map potential drug resistance mutations.",-1),d=[o,r];function l(c,u,h,p,f,m){return n(),i("div",null,d)}const _=t(s,[["render",l]]);export{v as __pageData,_ as default}; diff --git a/assets/papers_2019_dingens_b.md.ZMz_qDNq.js b/assets/papers_2019_dingens_b.md.C51xx5_b.js similarity index 97% rename from assets/papers_2019_dingens_b.md.ZMz_qDNq.js rename to assets/papers_2019_dingens_b.md.C51xx5_b.js index bd99c8f..50e8b58 100644 --- a/assets/papers_2019_dingens_b.md.ZMz_qDNq.js +++ b/assets/papers_2019_dingens_b.md.C51xx5_b.js @@ -1 +1 @@ -import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes","description":"","frontmatter":{"layout":"paper","title":"An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes","date":"2019-02-19","authors":["Adam S Dingens","Dana Arenz","Haidyn Weight","Julie Overbaugh","Jesse D Bloom"],"journal":"Immunity","doi":"10.1016/j.immuni.2018.12.017","link":"https://www.sciencedirect.com/science/article/pii/S107476131830565X?via%3Dihub","image":"/assets/papers/2019_dingens_b.jpg","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2019_dingens_b.md","filePath":"papers/2019_dingens_b.md"}'),s={name:"papers/2019_dingens_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Anti-HIV broadly neutralizing antibodies (bnAbs) have revealed vaccine targets on the virus’s envelope (Env) protein and are themselves promising immunotherapies. The efficacy of bnAb-based therapies and vaccines depends in part on how readily the virus can escape neutralization. Although structural studies can define contacts between bnAbs and Env, only functional studies can define mutations that confer escape. Here, we mapped how all possible single amino acid mutations in Env affect neutralization of HIV by nine bnAbs targeting five epitopes. For most bnAbs, mutations at only a small fraction of structurally defined contact sites mediated escape, and most escape occurred at sites near, but not in direct contact with, the antibody. The Env mutations selected by two pooled bnAbs were similar to those expected from the combination of the bnAbs’s independent action. Overall, our mutation-level antigenic atlas provides a comprehensive dataset for understanding viral immune escape and refining therapies and vaccines.",-1),c=[o,r];function d(l,p,u,b,m,h){return n(),t("div",null,c)}const _=a(s,[["render",d]]);export{g as __pageData,_ as default}; +import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes","description":"","frontmatter":{"layout":"paper","title":"An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes","date":"2019-02-19","authors":["Adam S Dingens","Dana Arenz","Haidyn Weight","Julie Overbaugh","Jesse D Bloom"],"journal":"Immunity","doi":"10.1016/j.immuni.2018.12.017","link":"https://www.sciencedirect.com/science/article/pii/S107476131830565X?via%3Dihub","image":"/assets/papers/2019_dingens_b.jpg","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2019_dingens_b.md","filePath":"papers/2019_dingens_b.md"}'),s={name:"papers/2019_dingens_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Anti-HIV broadly neutralizing antibodies (bnAbs) have revealed vaccine targets on the virus’s envelope (Env) protein and are themselves promising immunotherapies. The efficacy of bnAb-based therapies and vaccines depends in part on how readily the virus can escape neutralization. Although structural studies can define contacts between bnAbs and Env, only functional studies can define mutations that confer escape. Here, we mapped how all possible single amino acid mutations in Env affect neutralization of HIV by nine bnAbs targeting five epitopes. For most bnAbs, mutations at only a small fraction of structurally defined contact sites mediated escape, and most escape occurred at sites near, but not in direct contact with, the antibody. The Env mutations selected by two pooled bnAbs were similar to those expected from the combination of the bnAbs’s independent action. Overall, our mutation-level antigenic atlas provides a comprehensive dataset for understanding viral immune escape and refining therapies and vaccines.",-1),c=[o,r];function d(l,p,u,b,m,h){return n(),t("div",null,c)}const _=a(s,[["render",d]]);export{g as __pageData,_ as default}; diff --git a/assets/papers_2019_dingens_b.md.ZMz_qDNq.lean.js b/assets/papers_2019_dingens_b.md.C51xx5_b.lean.js similarity index 97% rename from assets/papers_2019_dingens_b.md.ZMz_qDNq.lean.js rename to assets/papers_2019_dingens_b.md.C51xx5_b.lean.js index bd99c8f..50e8b58 100644 --- a/assets/papers_2019_dingens_b.md.ZMz_qDNq.lean.js +++ b/assets/papers_2019_dingens_b.md.C51xx5_b.lean.js @@ -1 +1 @@ -import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes","description":"","frontmatter":{"layout":"paper","title":"An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes","date":"2019-02-19","authors":["Adam S Dingens","Dana Arenz","Haidyn Weight","Julie Overbaugh","Jesse D Bloom"],"journal":"Immunity","doi":"10.1016/j.immuni.2018.12.017","link":"https://www.sciencedirect.com/science/article/pii/S107476131830565X?via%3Dihub","image":"/assets/papers/2019_dingens_b.jpg","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2019_dingens_b.md","filePath":"papers/2019_dingens_b.md"}'),s={name:"papers/2019_dingens_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Anti-HIV broadly neutralizing antibodies (bnAbs) have revealed vaccine targets on the virus’s envelope (Env) protein and are themselves promising immunotherapies. The efficacy of bnAb-based therapies and vaccines depends in part on how readily the virus can escape neutralization. Although structural studies can define contacts between bnAbs and Env, only functional studies can define mutations that confer escape. Here, we mapped how all possible single amino acid mutations in Env affect neutralization of HIV by nine bnAbs targeting five epitopes. For most bnAbs, mutations at only a small fraction of structurally defined contact sites mediated escape, and most escape occurred at sites near, but not in direct contact with, the antibody. The Env mutations selected by two pooled bnAbs were similar to those expected from the combination of the bnAbs’s independent action. Overall, our mutation-level antigenic atlas provides a comprehensive dataset for understanding viral immune escape and refining therapies and vaccines.",-1),c=[o,r];function d(l,p,u,b,m,h){return n(),t("div",null,c)}const _=a(s,[["render",d]]);export{g as __pageData,_ as default}; +import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes","description":"","frontmatter":{"layout":"paper","title":"An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes","date":"2019-02-19","authors":["Adam S Dingens","Dana Arenz","Haidyn Weight","Julie Overbaugh","Jesse D Bloom"],"journal":"Immunity","doi":"10.1016/j.immuni.2018.12.017","link":"https://www.sciencedirect.com/science/article/pii/S107476131830565X?via%3Dihub","image":"/assets/papers/2019_dingens_b.jpg","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2019_dingens_b.md","filePath":"papers/2019_dingens_b.md"}'),s={name:"papers/2019_dingens_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Anti-HIV broadly neutralizing antibodies (bnAbs) have revealed vaccine targets on the virus’s envelope (Env) protein and are themselves promising immunotherapies. The efficacy of bnAb-based therapies and vaccines depends in part on how readily the virus can escape neutralization. Although structural studies can define contacts between bnAbs and Env, only functional studies can define mutations that confer escape. Here, we mapped how all possible single amino acid mutations in Env affect neutralization of HIV by nine bnAbs targeting five epitopes. For most bnAbs, mutations at only a small fraction of structurally defined contact sites mediated escape, and most escape occurred at sites near, but not in direct contact with, the antibody. The Env mutations selected by two pooled bnAbs were similar to those expected from the combination of the bnAbs’s independent action. Overall, our mutation-level antigenic atlas provides a comprehensive dataset for understanding viral immune escape and refining therapies and vaccines.",-1),c=[o,r];function d(l,p,u,b,m,h){return n(),t("div",null,c)}const _=a(s,[["render",d]]);export{g as __pageData,_ as default}; diff --git a/assets/papers_2019_lee.md.DB2ZDBaf.js b/assets/papers_2019_lee.md.BHzJxPUH.js similarity index 96% rename from assets/papers_2019_lee.md.DB2ZDBaf.js rename to assets/papers_2019_lee.md.BHzJxPUH.js index 5f44c35..f96766f 100644 --- a/assets/papers_2019_lee.md.DB2ZDBaf.js +++ b/assets/papers_2019_lee.md.BHzJxPUH.js @@ -1 +1 @@ -import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin","date":"2019-08-27","authors":["Juhye M Lee","Rachel Eguia","Seth J Zost","Saket Choudhary","Patrick C Wilson","Trevor Bedford","Terry Stevens-Ayers","Michael Boeckh","Aeron C Hurt","Seema S Lakdawala","Scott E Hensley","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.49324","link":"https://elifesciences.org/articles/49324","image":"/assets/papers/2019_lee.jpg","keywords":["Influenza","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2019_lee.md","filePath":"papers/2019_lee.md"}'),s={name:"papers/2019_lee.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"A longstanding question is how influenza virus evolves to escape human immunity, which is polyclonal and can target many distinct epitopes. Here, we map how all amino-acid mutations to influenza’s major surface protein affect viral neutralization by polyclonal human sera. The serum of some individuals is so focused that it selects single mutations that reduce viral neutralization by over an order of magnitude. However, different viral mutations escape the sera of different individuals. This individual-to-individual variation in viral escape mutations is not present among ferrets that have been infected just once with a defined viral strain. Our results show how different single mutations help influenza virus escape the immunity of different members of the human population, a phenomenon that could shape viral evolution and disease susceptibility.",-1),l=[o,r];function c(u,p,d,h,m,f){return i(),t("div",null,l)}const _=a(s,[["render",c]]);export{g as __pageData,_ as default}; +import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin","date":"2019-08-27","authors":["Juhye M Lee","Rachel Eguia","Seth J Zost","Saket Choudhary","Patrick C Wilson","Trevor Bedford","Terry Stevens-Ayers","Michael Boeckh","Aeron C Hurt","Seema S Lakdawala","Scott E Hensley","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.49324","link":"https://elifesciences.org/articles/49324","image":"/assets/papers/2019_lee.jpg","keywords":["Influenza","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2019_lee.md","filePath":"papers/2019_lee.md"}'),s={name:"papers/2019_lee.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"A longstanding question is how influenza virus evolves to escape human immunity, which is polyclonal and can target many distinct epitopes. Here, we map how all amino-acid mutations to influenza’s major surface protein affect viral neutralization by polyclonal human sera. The serum of some individuals is so focused that it selects single mutations that reduce viral neutralization by over an order of magnitude. However, different viral mutations escape the sera of different individuals. This individual-to-individual variation in viral escape mutations is not present among ferrets that have been infected just once with a defined viral strain. Our results show how different single mutations help influenza virus escape the immunity of different members of the human population, a phenomenon that could shape viral evolution and disease susceptibility.",-1),l=[o,r];function c(u,p,d,h,m,f){return i(),t("div",null,l)}const _=a(s,[["render",c]]);export{g as __pageData,_ as default}; diff --git a/assets/papers_2019_lee.md.DB2ZDBaf.lean.js b/assets/papers_2019_lee.md.BHzJxPUH.lean.js similarity index 96% rename from assets/papers_2019_lee.md.DB2ZDBaf.lean.js rename to assets/papers_2019_lee.md.BHzJxPUH.lean.js index 5f44c35..f96766f 100644 --- a/assets/papers_2019_lee.md.DB2ZDBaf.lean.js +++ b/assets/papers_2019_lee.md.BHzJxPUH.lean.js @@ -1 +1 @@ -import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin","date":"2019-08-27","authors":["Juhye M Lee","Rachel Eguia","Seth J Zost","Saket Choudhary","Patrick C Wilson","Trevor Bedford","Terry Stevens-Ayers","Michael Boeckh","Aeron C Hurt","Seema S Lakdawala","Scott E Hensley","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.49324","link":"https://elifesciences.org/articles/49324","image":"/assets/papers/2019_lee.jpg","keywords":["Influenza","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2019_lee.md","filePath":"papers/2019_lee.md"}'),s={name:"papers/2019_lee.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"A longstanding question is how influenza virus evolves to escape human immunity, which is polyclonal and can target many distinct epitopes. Here, we map how all amino-acid mutations to influenza’s major surface protein affect viral neutralization by polyclonal human sera. The serum of some individuals is so focused that it selects single mutations that reduce viral neutralization by over an order of magnitude. However, different viral mutations escape the sera of different individuals. This individual-to-individual variation in viral escape mutations is not present among ferrets that have been infected just once with a defined viral strain. Our results show how different single mutations help influenza virus escape the immunity of different members of the human population, a phenomenon that could shape viral evolution and disease susceptibility.",-1),l=[o,r];function c(u,p,d,h,m,f){return i(),t("div",null,l)}const _=a(s,[["render",c]]);export{g as __pageData,_ as default}; +import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin","date":"2019-08-27","authors":["Juhye M Lee","Rachel Eguia","Seth J Zost","Saket Choudhary","Patrick C Wilson","Trevor Bedford","Terry Stevens-Ayers","Michael Boeckh","Aeron C Hurt","Seema S Lakdawala","Scott E Hensley","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.49324","link":"https://elifesciences.org/articles/49324","image":"/assets/papers/2019_lee.jpg","keywords":["Influenza","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2019_lee.md","filePath":"papers/2019_lee.md"}'),s={name:"papers/2019_lee.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"A longstanding question is how influenza virus evolves to escape human immunity, which is polyclonal and can target many distinct epitopes. Here, we map how all amino-acid mutations to influenza’s major surface protein affect viral neutralization by polyclonal human sera. The serum of some individuals is so focused that it selects single mutations that reduce viral neutralization by over an order of magnitude. However, different viral mutations escape the sera of different individuals. This individual-to-individual variation in viral escape mutations is not present among ferrets that have been infected just once with a defined viral strain. Our results show how different single mutations help influenza virus escape the immunity of different members of the human population, a phenomenon that could shape viral evolution and disease susceptibility.",-1),l=[o,r];function c(u,p,d,h,m,f){return i(),t("div",null,l)}const _=a(s,[["render",c]]);export{g as __pageData,_ as default}; diff --git a/assets/papers_2019_machkovech.md.zTr1zOuH.js b/assets/papers_2019_machkovech.md.lJ_oB7Fz.js similarity index 97% rename from assets/papers_2019_machkovech.md.zTr1zOuH.js rename to assets/papers_2019_machkovech.md.lJ_oB7Fz.js index 1bb1516..b0839fa 100644 --- a/assets/papers_2019_machkovech.md.zTr1zOuH.js +++ b/assets/papers_2019_machkovech.md.lJ_oB7Fz.js @@ -1 +1 @@ -import{_ as t,c as i,o as a,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Comprehensive profiling of translation initiation in influenza virus infected cells","description":"","frontmatter":{"layout":"paper","title":"Comprehensive profiling of translation initiation in influenza virus infected cells","date":"2019-01-23","authors":["Heather M Machkovech","Jesse D Bloom","Arvind R Subramaniam"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1007518","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007518","image":"/assets/papers/2019_machkovech.png","keywords":["Influenza"]},"headers":[],"relativePath":"papers/2019_machkovech.md","filePath":"papers/2019_machkovech.md"}'),s={name:"papers/2019_machkovech.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Translation can initiate at alternate, non-canonical start codons in response to stressful stimuli in mammalian cells. Recent studies suggest that viral infection and anti-viral responses alter sites of translation initiation, and in some cases, lead to production of novel immune epitopes. Here we systematically investigate the extent and impact of alternate translation initiation in cells infected with influenza virus. We perform evolutionary analyses that suggest selection against non-canonical initiation at CUG codons in influenza virus lineages that have adapted to mammalian hosts. We then use ribosome profiling with the initiation inhibitor lactimidomycin to experimentally delineate translation initiation sites in a human lung epithelial cell line infected with influenza virus. We identify several candidate sites of alternate initiation in influenza mRNAs, all of which occur at AUG codons that are downstream of canonical initiation codons. One of these candidate downstream start sites truncates 14 amino acids from the N-terminus of the N1 neuraminidase protein, resulting in loss of its cytoplasmic tail and a portion of the transmembrane domain. This truncated neuraminidase protein is expressed on the cell surface during influenza virus infection, is enzymatically active, and is conserved in most N1 viral lineages. We do not detect globally higher levels of alternate translation initiation on host transcripts upon influenza infection or during the anti-viral response, but the subset of host transcripts induced by the anti-viral response is enriched for alternate initiation sites. Together, our results systematically map the landscape of translation initiation during influenza virus infection, and shed light on the evolutionary forces shaping this landscape.",-1),l=[o,r];function c(d,h,p,u,m,f){return a(),i("div",null,l)}const _=t(s,[["render",c]]);export{g as __pageData,_ as default}; +import{_ as t,c as i,o as a,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Comprehensive profiling of translation initiation in influenza virus infected cells","description":"","frontmatter":{"layout":"paper","title":"Comprehensive profiling of translation initiation in influenza virus infected cells","date":"2019-01-23","authors":["Heather M Machkovech","Jesse D Bloom","Arvind R Subramaniam"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1007518","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007518","image":"/assets/papers/2019_machkovech.png","keywords":["Influenza"]},"headers":[],"relativePath":"papers/2019_machkovech.md","filePath":"papers/2019_machkovech.md"}'),s={name:"papers/2019_machkovech.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Translation can initiate at alternate, non-canonical start codons in response to stressful stimuli in mammalian cells. Recent studies suggest that viral infection and anti-viral responses alter sites of translation initiation, and in some cases, lead to production of novel immune epitopes. Here we systematically investigate the extent and impact of alternate translation initiation in cells infected with influenza virus. We perform evolutionary analyses that suggest selection against non-canonical initiation at CUG codons in influenza virus lineages that have adapted to mammalian hosts. We then use ribosome profiling with the initiation inhibitor lactimidomycin to experimentally delineate translation initiation sites in a human lung epithelial cell line infected with influenza virus. We identify several candidate sites of alternate initiation in influenza mRNAs, all of which occur at AUG codons that are downstream of canonical initiation codons. One of these candidate downstream start sites truncates 14 amino acids from the N-terminus of the N1 neuraminidase protein, resulting in loss of its cytoplasmic tail and a portion of the transmembrane domain. This truncated neuraminidase protein is expressed on the cell surface during influenza virus infection, is enzymatically active, and is conserved in most N1 viral lineages. We do not detect globally higher levels of alternate translation initiation on host transcripts upon influenza infection or during the anti-viral response, but the subset of host transcripts induced by the anti-viral response is enriched for alternate initiation sites. Together, our results systematically map the landscape of translation initiation during influenza virus infection, and shed light on the evolutionary forces shaping this landscape.",-1),l=[o,r];function c(d,h,p,u,m,f){return a(),i("div",null,l)}const _=t(s,[["render",c]]);export{g as __pageData,_ as default}; diff --git a/assets/papers_2019_machkovech.md.zTr1zOuH.lean.js b/assets/papers_2019_machkovech.md.lJ_oB7Fz.lean.js similarity index 97% rename from assets/papers_2019_machkovech.md.zTr1zOuH.lean.js rename to assets/papers_2019_machkovech.md.lJ_oB7Fz.lean.js index 1bb1516..b0839fa 100644 --- a/assets/papers_2019_machkovech.md.zTr1zOuH.lean.js +++ b/assets/papers_2019_machkovech.md.lJ_oB7Fz.lean.js @@ -1 +1 @@ -import{_ as t,c as i,o as a,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Comprehensive profiling of translation initiation in influenza virus infected cells","description":"","frontmatter":{"layout":"paper","title":"Comprehensive profiling of translation initiation in influenza virus infected cells","date":"2019-01-23","authors":["Heather M Machkovech","Jesse D Bloom","Arvind R Subramaniam"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1007518","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007518","image":"/assets/papers/2019_machkovech.png","keywords":["Influenza"]},"headers":[],"relativePath":"papers/2019_machkovech.md","filePath":"papers/2019_machkovech.md"}'),s={name:"papers/2019_machkovech.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Translation can initiate at alternate, non-canonical start codons in response to stressful stimuli in mammalian cells. Recent studies suggest that viral infection and anti-viral responses alter sites of translation initiation, and in some cases, lead to production of novel immune epitopes. Here we systematically investigate the extent and impact of alternate translation initiation in cells infected with influenza virus. We perform evolutionary analyses that suggest selection against non-canonical initiation at CUG codons in influenza virus lineages that have adapted to mammalian hosts. We then use ribosome profiling with the initiation inhibitor lactimidomycin to experimentally delineate translation initiation sites in a human lung epithelial cell line infected with influenza virus. We identify several candidate sites of alternate initiation in influenza mRNAs, all of which occur at AUG codons that are downstream of canonical initiation codons. One of these candidate downstream start sites truncates 14 amino acids from the N-terminus of the N1 neuraminidase protein, resulting in loss of its cytoplasmic tail and a portion of the transmembrane domain. This truncated neuraminidase protein is expressed on the cell surface during influenza virus infection, is enzymatically active, and is conserved in most N1 viral lineages. We do not detect globally higher levels of alternate translation initiation on host transcripts upon influenza infection or during the anti-viral response, but the subset of host transcripts induced by the anti-viral response is enriched for alternate initiation sites. Together, our results systematically map the landscape of translation initiation during influenza virus infection, and shed light on the evolutionary forces shaping this landscape.",-1),l=[o,r];function c(d,h,p,u,m,f){return a(),i("div",null,l)}const _=t(s,[["render",c]]);export{g as __pageData,_ as default}; +import{_ as t,c as i,o as a,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Comprehensive profiling of translation initiation in influenza virus infected cells","description":"","frontmatter":{"layout":"paper","title":"Comprehensive profiling of translation initiation in influenza virus infected cells","date":"2019-01-23","authors":["Heather M Machkovech","Jesse D Bloom","Arvind R Subramaniam"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1007518","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007518","image":"/assets/papers/2019_machkovech.png","keywords":["Influenza"]},"headers":[],"relativePath":"papers/2019_machkovech.md","filePath":"papers/2019_machkovech.md"}'),s={name:"papers/2019_machkovech.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Translation can initiate at alternate, non-canonical start codons in response to stressful stimuli in mammalian cells. Recent studies suggest that viral infection and anti-viral responses alter sites of translation initiation, and in some cases, lead to production of novel immune epitopes. Here we systematically investigate the extent and impact of alternate translation initiation in cells infected with influenza virus. We perform evolutionary analyses that suggest selection against non-canonical initiation at CUG codons in influenza virus lineages that have adapted to mammalian hosts. We then use ribosome profiling with the initiation inhibitor lactimidomycin to experimentally delineate translation initiation sites in a human lung epithelial cell line infected with influenza virus. We identify several candidate sites of alternate initiation in influenza mRNAs, all of which occur at AUG codons that are downstream of canonical initiation codons. One of these candidate downstream start sites truncates 14 amino acids from the N-terminus of the N1 neuraminidase protein, resulting in loss of its cytoplasmic tail and a portion of the transmembrane domain. This truncated neuraminidase protein is expressed on the cell surface during influenza virus infection, is enzymatically active, and is conserved in most N1 viral lineages. We do not detect globally higher levels of alternate translation initiation on host transcripts upon influenza infection or during the anti-viral response, but the subset of host transcripts induced by the anti-viral response is enriched for alternate initiation sites. Together, our results systematically map the landscape of translation initiation during influenza virus infection, and shed light on the evolutionary forces shaping this landscape.",-1),l=[o,r];function c(d,h,p,u,m,f){return a(),i("div",null,l)}const _=t(s,[["render",c]]);export{g as __pageData,_ as default}; diff --git a/assets/papers_2019_russell.md.kcwDWF1T.js b/assets/papers_2019_russell.md.CDGyoaHs.js similarity index 97% rename from assets/papers_2019_russell.md.kcwDWF1T.js rename to assets/papers_2019_russell.md.CDGyoaHs.js index 8689f09..601ec6e 100644 --- a/assets/papers_2019_russell.md.kcwDWF1T.js +++ b/assets/papers_2019_russell.md.CDGyoaHs.js @@ -1 +1 @@ -import{_ as t,c as i,o as n,b as e,d as s}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Single-cell virus sequencing of influenza infections that trigger innate immunity","description":"","frontmatter":{"layout":"paper","title":"Single-cell virus sequencing of influenza infections that trigger innate immunity","date":"2019-07-15","authors":["Alistair B Russell","Elizaveta Elshina","Jacob R Kowalsky","Aartjan JW Te Velthuis","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.00500-19","link":"https://journals.asm.org/doi/full/10.1128/jvi.00500-19","image":"/assets/papers/2019_russell.jpg","keywords":["Influenza","Single-cell sequencing"]},"headers":[],"relativePath":"papers/2019_russell.md","filePath":"papers/2019_russell.md"}'),a={name:"papers/2019_russell.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza virus-infected cells vary widely in their expression of viral genes and only occasionally activate innate immunity. Here, we develop a new method to assess how the genetic variation in viral populations contributes to this heterogeneity. We do this by determining the transcriptome and full-length sequences of all viral genes in single cells infected with a nominally “pure” stock of influenza virus. Most cells are infected by virions with defects, some of which increase the frequency of innate-immune activation. These immunostimulatory defects are diverse and include mutations that perturb the function of the viral polymerase protein PB1, large internal deletions in viral genes, and failure to express the virus’s interferon antagonist NS1. However, immune activation remains stochastic in cells infected by virions with these defects and occasionally is triggered even by virions that express unmutated copies of all genes. Our work shows that the diverse spectrum of defects in influenza virus populations contributes to—but does not completely explain—the heterogeneity in viral gene expression and immune activation in single infected cells.",-1),l=[o,r];function c(u,d,h,f,p,m){return n(),i("div",null,l)}const y=t(a,[["render",c]]);export{g as __pageData,y as default}; +import{_ as t,c as i,o as n,b as e,d as s}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Single-cell virus sequencing of influenza infections that trigger innate immunity","description":"","frontmatter":{"layout":"paper","title":"Single-cell virus sequencing of influenza infections that trigger innate immunity","date":"2019-07-15","authors":["Alistair B Russell","Elizaveta Elshina","Jacob R Kowalsky","Aartjan JW Te Velthuis","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.00500-19","link":"https://journals.asm.org/doi/full/10.1128/jvi.00500-19","image":"/assets/papers/2019_russell.jpg","keywords":["Influenza","Single-cell sequencing"]},"headers":[],"relativePath":"papers/2019_russell.md","filePath":"papers/2019_russell.md"}'),a={name:"papers/2019_russell.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza virus-infected cells vary widely in their expression of viral genes and only occasionally activate innate immunity. Here, we develop a new method to assess how the genetic variation in viral populations contributes to this heterogeneity. We do this by determining the transcriptome and full-length sequences of all viral genes in single cells infected with a nominally “pure” stock of influenza virus. Most cells are infected by virions with defects, some of which increase the frequency of innate-immune activation. These immunostimulatory defects are diverse and include mutations that perturb the function of the viral polymerase protein PB1, large internal deletions in viral genes, and failure to express the virus’s interferon antagonist NS1. However, immune activation remains stochastic in cells infected by virions with these defects and occasionally is triggered even by virions that express unmutated copies of all genes. Our work shows that the diverse spectrum of defects in influenza virus populations contributes to—but does not completely explain—the heterogeneity in viral gene expression and immune activation in single infected cells.",-1),l=[o,r];function c(u,d,h,f,p,m){return n(),i("div",null,l)}const y=t(a,[["render",c]]);export{g as __pageData,y as default}; diff --git a/assets/papers_2019_russell.md.kcwDWF1T.lean.js b/assets/papers_2019_russell.md.CDGyoaHs.lean.js similarity index 97% rename from assets/papers_2019_russell.md.kcwDWF1T.lean.js rename to assets/papers_2019_russell.md.CDGyoaHs.lean.js index 8689f09..601ec6e 100644 --- a/assets/papers_2019_russell.md.kcwDWF1T.lean.js +++ b/assets/papers_2019_russell.md.CDGyoaHs.lean.js @@ -1 +1 @@ -import{_ as t,c as i,o as n,b as e,d as s}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Single-cell virus sequencing of influenza infections that trigger innate immunity","description":"","frontmatter":{"layout":"paper","title":"Single-cell virus sequencing of influenza infections that trigger innate immunity","date":"2019-07-15","authors":["Alistair B Russell","Elizaveta Elshina","Jacob R Kowalsky","Aartjan JW Te Velthuis","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.00500-19","link":"https://journals.asm.org/doi/full/10.1128/jvi.00500-19","image":"/assets/papers/2019_russell.jpg","keywords":["Influenza","Single-cell sequencing"]},"headers":[],"relativePath":"papers/2019_russell.md","filePath":"papers/2019_russell.md"}'),a={name:"papers/2019_russell.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza virus-infected cells vary widely in their expression of viral genes and only occasionally activate innate immunity. Here, we develop a new method to assess how the genetic variation in viral populations contributes to this heterogeneity. We do this by determining the transcriptome and full-length sequences of all viral genes in single cells infected with a nominally “pure” stock of influenza virus. Most cells are infected by virions with defects, some of which increase the frequency of innate-immune activation. These immunostimulatory defects are diverse and include mutations that perturb the function of the viral polymerase protein PB1, large internal deletions in viral genes, and failure to express the virus’s interferon antagonist NS1. However, immune activation remains stochastic in cells infected by virions with these defects and occasionally is triggered even by virions that express unmutated copies of all genes. Our work shows that the diverse spectrum of defects in influenza virus populations contributes to—but does not completely explain—the heterogeneity in viral gene expression and immune activation in single infected cells.",-1),l=[o,r];function c(u,d,h,f,p,m){return n(),i("div",null,l)}const y=t(a,[["render",c]]);export{g as __pageData,y as default}; +import{_ as t,c as i,o as n,b as e,d as s}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Single-cell virus sequencing of influenza infections that trigger innate immunity","description":"","frontmatter":{"layout":"paper","title":"Single-cell virus sequencing of influenza infections that trigger innate immunity","date":"2019-07-15","authors":["Alistair B Russell","Elizaveta Elshina","Jacob R Kowalsky","Aartjan JW Te Velthuis","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.00500-19","link":"https://journals.asm.org/doi/full/10.1128/jvi.00500-19","image":"/assets/papers/2019_russell.jpg","keywords":["Influenza","Single-cell sequencing"]},"headers":[],"relativePath":"papers/2019_russell.md","filePath":"papers/2019_russell.md"}'),a={name:"papers/2019_russell.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza virus-infected cells vary widely in their expression of viral genes and only occasionally activate innate immunity. Here, we develop a new method to assess how the genetic variation in viral populations contributes to this heterogeneity. We do this by determining the transcriptome and full-length sequences of all viral genes in single cells infected with a nominally “pure” stock of influenza virus. Most cells are infected by virions with defects, some of which increase the frequency of innate-immune activation. These immunostimulatory defects are diverse and include mutations that perturb the function of the viral polymerase protein PB1, large internal deletions in viral genes, and failure to express the virus’s interferon antagonist NS1. However, immune activation remains stochastic in cells infected by virions with these defects and occasionally is triggered even by virions that express unmutated copies of all genes. Our work shows that the diverse spectrum of defects in influenza virus populations contributes to—but does not completely explain—the heterogeneity in viral gene expression and immune activation in single infected cells.",-1),l=[o,r];function c(u,d,h,f,p,m){return n(),i("div",null,l)}const y=t(a,[["render",c]]);export{g as __pageData,y as default}; diff --git a/assets/papers_2019_soh.md.ChLrrY3X.js b/assets/papers_2019_soh.md.Bf5D9w2H.js similarity index 93% rename from assets/papers_2019_soh.md.ChLrrY3X.js rename to assets/papers_2019_soh.md.Bf5D9w2H.js index 876ad92..1a6b22d 100644 --- a/assets/papers_2019_soh.md.ChLrrY3X.js +++ b/assets/papers_2019_soh.md.Bf5D9w2H.js @@ -1 +1 @@ -import{_ as a,c as t,o,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans","description":"","frontmatter":{"layout":"paper","title":"Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans","date":"2019-04-30","authors":["YQ Shirleen Soh","Louise H Moncla","Rachel Eguia","Trevor Bedford","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.45079","link":"https://doi.org/10.7554/eLife.45079","image":"/assets/papers/2019_soh.jpg","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2019_soh.md","filePath":"papers/2019_soh.md"}'),s={name:"papers/2019_soh.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Viruses like influenza are infamous for their ability to adapt to new hosts. Retrospective studies of natural zoonoses and passaging in the lab have identified a modest number of host-adaptive mutations. However, it is unclear if these mutations represent all ways that influenza can adapt to a new host. Here we take a prospective approach to this question by completely mapping amino-acid mutations to the avian influenza virus polymerase protein PB2 that enhance growth in human cells. We identify numerous previously uncharacterized human-adaptive mutations. These mutations cluster on PB2’s surface, highlighting potential interfaces with host factors. Some previously uncharacterized adaptive mutations occur in avian-to-human transmission of H7N9 influenza, showing their importance for natural virus evolution. But other adaptive mutations do not occur in nature because they are inaccessible via single-nucleotide mutations. Overall, our work shows how selection at key molecular surfaces combines with evolutionary accessibility to shape viral host adaptation.",-1),l=[n,r];function c(h,p,u,d,m,f){return o(),t("div",null,l)}const g=a(s,[["render",c]]);export{_ as __pageData,g as default}; +import{_ as a,c as t,o,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans","description":"","frontmatter":{"layout":"paper","title":"Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans","date":"2019-04-30","authors":["YQ Shirleen Soh","Louise H Moncla","Rachel Eguia","Trevor Bedford","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.45079","link":"https://doi.org/10.7554/eLife.45079","image":"/assets/papers/2019_soh.jpg","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2019_soh.md","filePath":"papers/2019_soh.md"}'),s={name:"papers/2019_soh.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Viruses like influenza are infamous for their ability to adapt to new hosts. Retrospective studies of natural zoonoses and passaging in the lab have identified a modest number of host-adaptive mutations. However, it is unclear if these mutations represent all ways that influenza can adapt to a new host. Here we take a prospective approach to this question by completely mapping amino-acid mutations to the avian influenza virus polymerase protein PB2 that enhance growth in human cells. We identify numerous previously uncharacterized human-adaptive mutations. These mutations cluster on PB2’s surface, highlighting potential interfaces with host factors. Some previously uncharacterized adaptive mutations occur in avian-to-human transmission of H7N9 influenza, showing their importance for natural virus evolution. But other adaptive mutations do not occur in nature because they are inaccessible via single-nucleotide mutations. Overall, our work shows how selection at key molecular surfaces combines with evolutionary accessibility to shape viral host adaptation.",-1),l=[n,r];function c(h,p,u,d,m,f){return o(),t("div",null,l)}const g=a(s,[["render",c]]);export{_ as __pageData,g as default}; diff --git a/assets/papers_2019_soh.md.ChLrrY3X.lean.js b/assets/papers_2019_soh.md.Bf5D9w2H.lean.js similarity index 93% rename from assets/papers_2019_soh.md.ChLrrY3X.lean.js rename to assets/papers_2019_soh.md.Bf5D9w2H.lean.js index 876ad92..1a6b22d 100644 --- a/assets/papers_2019_soh.md.ChLrrY3X.lean.js +++ b/assets/papers_2019_soh.md.Bf5D9w2H.lean.js @@ -1 +1 @@ -import{_ as a,c as t,o,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans","description":"","frontmatter":{"layout":"paper","title":"Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans","date":"2019-04-30","authors":["YQ Shirleen Soh","Louise H Moncla","Rachel Eguia","Trevor Bedford","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.45079","link":"https://doi.org/10.7554/eLife.45079","image":"/assets/papers/2019_soh.jpg","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2019_soh.md","filePath":"papers/2019_soh.md"}'),s={name:"papers/2019_soh.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Viruses like influenza are infamous for their ability to adapt to new hosts. Retrospective studies of natural zoonoses and passaging in the lab have identified a modest number of host-adaptive mutations. However, it is unclear if these mutations represent all ways that influenza can adapt to a new host. Here we take a prospective approach to this question by completely mapping amino-acid mutations to the avian influenza virus polymerase protein PB2 that enhance growth in human cells. We identify numerous previously uncharacterized human-adaptive mutations. These mutations cluster on PB2’s surface, highlighting potential interfaces with host factors. Some previously uncharacterized adaptive mutations occur in avian-to-human transmission of H7N9 influenza, showing their importance for natural virus evolution. But other adaptive mutations do not occur in nature because they are inaccessible via single-nucleotide mutations. Overall, our work shows how selection at key molecular surfaces combines with evolutionary accessibility to shape viral host adaptation.",-1),l=[n,r];function c(h,p,u,d,m,f){return o(),t("div",null,l)}const g=a(s,[["render",c]]);export{_ as __pageData,g as default}; +import{_ as a,c as t,o,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans","description":"","frontmatter":{"layout":"paper","title":"Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans","date":"2019-04-30","authors":["YQ Shirleen Soh","Louise H Moncla","Rachel Eguia","Trevor Bedford","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.45079","link":"https://doi.org/10.7554/eLife.45079","image":"/assets/papers/2019_soh.jpg","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2019_soh.md","filePath":"papers/2019_soh.md"}'),s={name:"papers/2019_soh.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Viruses like influenza are infamous for their ability to adapt to new hosts. Retrospective studies of natural zoonoses and passaging in the lab have identified a modest number of host-adaptive mutations. However, it is unclear if these mutations represent all ways that influenza can adapt to a new host. Here we take a prospective approach to this question by completely mapping amino-acid mutations to the avian influenza virus polymerase protein PB2 that enhance growth in human cells. We identify numerous previously uncharacterized human-adaptive mutations. These mutations cluster on PB2’s surface, highlighting potential interfaces with host factors. Some previously uncharacterized adaptive mutations occur in avian-to-human transmission of H7N9 influenza, showing their importance for natural virus evolution. But other adaptive mutations do not occur in nature because they are inaccessible via single-nucleotide mutations. Overall, our work shows how selection at key molecular surfaces combines with evolutionary accessibility to shape viral host adaptation.",-1),l=[n,r];function c(h,p,u,d,m,f){return o(),t("div",null,l)}const g=a(s,[["render",c]]);export{_ as __pageData,g as default}; diff --git a/assets/papers_2019_xue_a.md.CXVQwdaw.js b/assets/papers_2019_xue_a.md.BmTcPROU.js similarity index 97% rename from assets/papers_2019_xue_a.md.CXVQwdaw.js rename to assets/papers_2019_xue_a.md.BmTcPROU.js index 981990a..b2b7f09 100644 --- a/assets/papers_2019_xue_a.md.CXVQwdaw.js +++ b/assets/papers_2019_xue_a.md.BmTcPROU.js @@ -1 +1 @@ -import{_ as t,c as i,o as a,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const v=JSON.parse('{"title":"Reconciling disparate estimates of viral genetic diversity during human influenza infections","description":"","frontmatter":{"layout":"paper","title":"Reconciling disparate estimates of viral genetic diversity during human influenza infections","date":"2019-09-01","authors":["Katherine S Xue","Jesse D Bloom"],"journal":"Nature genetics","doi":"10.1038/s41588-019-0349-3","link":"https://www.nature.com/articles/s41588-019-0349-3","image":"/assets/papers/2019_xue_a.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2019_xue_a.md","filePath":"papers/2019_xue_a.md"}'),s={name:"papers/2019_xue_a.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"To the Editor — A key question in the study of influenza virus evolution is how rapidly viral genetic variation arises within infected humans1,2. Recently, several studies have measured influenza’s within-host genetic diversity in large cohorts of infected humans through high-throughput deep sequencing3,4,5,6 (Supplementary Table 1). These studies disagree in their estimates of influenza’s within-host genetic diversity. In a Nature Genetics letter titled ‘Quantifying influenza virus diversity and transmission in humans’, analyzing a household cohort in Hong Kong, Poon et al.4 have estimated that within-host genetic diversity is high, and 200–250 viral genomes are transmitted between individuals. However, several recent studies conducted in Wisconsin3, Michigan6, and Washington7 that used similar methodologies have estimated lower levels of viral genetic diversity. In particular, the Michigan study has estimated a narrow transmission bottleneck of just one or two viral genomes6. We sought to examine whether technical differences in the underlying deep-sequencing datasets or the methods used to analyze them might explain the disparate estimates of within-host viral genetic diversity. We identified an anomaly in the Hong Kong data that provides a technical explanation for these discrepancies: read pairs from this study are often split between different biological samples, thus indicating that some reads are incorrectly assigned.",-1),d=[r,o];function h(l,c,u,g,m,p){return a(),i("div",null,d)}const _=t(s,[["render",h]]);export{v as __pageData,_ as default}; +import{_ as t,c as i,o as a,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const v=JSON.parse('{"title":"Reconciling disparate estimates of viral genetic diversity during human influenza infections","description":"","frontmatter":{"layout":"paper","title":"Reconciling disparate estimates of viral genetic diversity during human influenza infections","date":"2019-09-01","authors":["Katherine S Xue","Jesse D Bloom"],"journal":"Nature genetics","doi":"10.1038/s41588-019-0349-3","link":"https://www.nature.com/articles/s41588-019-0349-3","image":"/assets/papers/2019_xue_a.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2019_xue_a.md","filePath":"papers/2019_xue_a.md"}'),s={name:"papers/2019_xue_a.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"To the Editor — A key question in the study of influenza virus evolution is how rapidly viral genetic variation arises within infected humans1,2. Recently, several studies have measured influenza’s within-host genetic diversity in large cohorts of infected humans through high-throughput deep sequencing3,4,5,6 (Supplementary Table 1). These studies disagree in their estimates of influenza’s within-host genetic diversity. In a Nature Genetics letter titled ‘Quantifying influenza virus diversity and transmission in humans’, analyzing a household cohort in Hong Kong, Poon et al.4 have estimated that within-host genetic diversity is high, and 200–250 viral genomes are transmitted between individuals. However, several recent studies conducted in Wisconsin3, Michigan6, and Washington7 that used similar methodologies have estimated lower levels of viral genetic diversity. In particular, the Michigan study has estimated a narrow transmission bottleneck of just one or two viral genomes6. We sought to examine whether technical differences in the underlying deep-sequencing datasets or the methods used to analyze them might explain the disparate estimates of within-host viral genetic diversity. We identified an anomaly in the Hong Kong data that provides a technical explanation for these discrepancies: read pairs from this study are often split between different biological samples, thus indicating that some reads are incorrectly assigned.",-1),d=[r,o];function h(l,c,u,g,m,p){return a(),i("div",null,d)}const _=t(s,[["render",h]]);export{v as __pageData,_ as default}; diff --git a/assets/papers_2019_xue_a.md.CXVQwdaw.lean.js b/assets/papers_2019_xue_a.md.BmTcPROU.lean.js similarity index 97% rename from assets/papers_2019_xue_a.md.CXVQwdaw.lean.js rename to assets/papers_2019_xue_a.md.BmTcPROU.lean.js index 981990a..b2b7f09 100644 --- a/assets/papers_2019_xue_a.md.CXVQwdaw.lean.js +++ b/assets/papers_2019_xue_a.md.BmTcPROU.lean.js @@ -1 +1 @@ -import{_ as t,c as i,o as a,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const v=JSON.parse('{"title":"Reconciling disparate estimates of viral genetic diversity during human influenza infections","description":"","frontmatter":{"layout":"paper","title":"Reconciling disparate estimates of viral genetic diversity during human influenza infections","date":"2019-09-01","authors":["Katherine S Xue","Jesse D Bloom"],"journal":"Nature genetics","doi":"10.1038/s41588-019-0349-3","link":"https://www.nature.com/articles/s41588-019-0349-3","image":"/assets/papers/2019_xue_a.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2019_xue_a.md","filePath":"papers/2019_xue_a.md"}'),s={name:"papers/2019_xue_a.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"To the Editor — A key question in the study of influenza virus evolution is how rapidly viral genetic variation arises within infected humans1,2. Recently, several studies have measured influenza’s within-host genetic diversity in large cohorts of infected humans through high-throughput deep sequencing3,4,5,6 (Supplementary Table 1). These studies disagree in their estimates of influenza’s within-host genetic diversity. In a Nature Genetics letter titled ‘Quantifying influenza virus diversity and transmission in humans’, analyzing a household cohort in Hong Kong, Poon et al.4 have estimated that within-host genetic diversity is high, and 200–250 viral genomes are transmitted between individuals. However, several recent studies conducted in Wisconsin3, Michigan6, and Washington7 that used similar methodologies have estimated lower levels of viral genetic diversity. In particular, the Michigan study has estimated a narrow transmission bottleneck of just one or two viral genomes6. We sought to examine whether technical differences in the underlying deep-sequencing datasets or the methods used to analyze them might explain the disparate estimates of within-host viral genetic diversity. We identified an anomaly in the Hong Kong data that provides a technical explanation for these discrepancies: read pairs from this study are often split between different biological samples, thus indicating that some reads are incorrectly assigned.",-1),d=[r,o];function h(l,c,u,g,m,p){return a(),i("div",null,d)}const _=t(s,[["render",h]]);export{v as __pageData,_ as default}; +import{_ as t,c as i,o as a,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const v=JSON.parse('{"title":"Reconciling disparate estimates of viral genetic diversity during human influenza infections","description":"","frontmatter":{"layout":"paper","title":"Reconciling disparate estimates of viral genetic diversity during human influenza infections","date":"2019-09-01","authors":["Katherine S Xue","Jesse D Bloom"],"journal":"Nature genetics","doi":"10.1038/s41588-019-0349-3","link":"https://www.nature.com/articles/s41588-019-0349-3","image":"/assets/papers/2019_xue_a.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2019_xue_a.md","filePath":"papers/2019_xue_a.md"}'),s={name:"papers/2019_xue_a.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"To the Editor — A key question in the study of influenza virus evolution is how rapidly viral genetic variation arises within infected humans1,2. Recently, several studies have measured influenza’s within-host genetic diversity in large cohorts of infected humans through high-throughput deep sequencing3,4,5,6 (Supplementary Table 1). These studies disagree in their estimates of influenza’s within-host genetic diversity. In a Nature Genetics letter titled ‘Quantifying influenza virus diversity and transmission in humans’, analyzing a household cohort in Hong Kong, Poon et al.4 have estimated that within-host genetic diversity is high, and 200–250 viral genomes are transmitted between individuals. However, several recent studies conducted in Wisconsin3, Michigan6, and Washington7 that used similar methodologies have estimated lower levels of viral genetic diversity. In particular, the Michigan study has estimated a narrow transmission bottleneck of just one or two viral genomes6. We sought to examine whether technical differences in the underlying deep-sequencing datasets or the methods used to analyze them might explain the disparate estimates of within-host viral genetic diversity. We identified an anomaly in the Hong Kong data that provides a technical explanation for these discrepancies: read pairs from this study are often split between different biological samples, thus indicating that some reads are incorrectly assigned.",-1),d=[r,o];function h(l,c,u,g,m,p){return a(),i("div",null,d)}const _=t(s,[["render",h]]);export{v as __pageData,_ as default}; diff --git a/assets/papers_2020_crawford.md.pF0wWDFV.js b/assets/papers_2020_crawford.md.COKdMTcD.js similarity index 97% rename from assets/papers_2020_crawford.md.pF0wWDFV.js rename to assets/papers_2020_crawford.md.COKdMTcD.js index 0e66812..9d575ce 100644 --- a/assets/papers_2020_crawford.md.pF0wWDFV.js +++ b/assets/papers_2020_crawford.md.COKdMTcD.js @@ -1 +1 @@ -import{_ as a,c as t,o as i,b as e,d as r}from"./chunks/framework.BqSDeblO.js";const v=JSON.parse('{"title":"Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays","description":"","frontmatter":{"layout":"paper","title":"Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays","date":"2020-05-06","authors":["Katharine HD Crawford","Rachel Eguia","Adam S Dingens","Andrea N Loes","Keara D Malone","Caitlin R Wolf","Helen Y Chu","M Alejandra Tortorici","David Veesler","Michael Murphy","Deleah Pettie","Neil P King","Alejandro B Balazs","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12050513","link":"https://www.mdpi.com/1999-4915/12/5/513","image":"/assets/papers/2020_crawford.jpg","keywords":["SARS-CoV-2","Immunity","Pseudovirus"]},"headers":[],"relativePath":"papers/2020_crawford.md","filePath":"papers/2020_crawford.md"}'),s={name:"papers/2020_crawford.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"SARS-CoV-2 enters cells using its Spike protein, which is also the main target of neutralizing antibodies. Therefore, assays to measure how antibodies and sera affect Spike-mediated viral infection are important for studying immunity. Because SARS-CoV-2 is a biosafety-level-3 virus, one way to simplify such assays is to pseudotype biosafety-level-2 viral particles with Spike. Such pseudotyping has now been described for single-cycle lentiviral, retroviral, and vesicular stomatitis virus (VSV) particles, but the reagents and protocols are not widely available. Here, we detailed how to effectively pseudotype lentiviral particles with SARS-CoV-2 Spike and infect 293T cells engineered to express the SARS-CoV-2 receptor, ACE2. We also made all the key experimental reagents available in the BEI Resources repository of ATCC and the NIH. Furthermore, we demonstrated how these pseudotyped lentiviral particles could be used to measure the neutralizing activity of human sera or plasma against SARS-CoV-2 in convenient luciferase-based assays, thereby providing a valuable complement to ELISA-based methods that measure antibody binding rather than neutralization.",-1),l=[o,n];function d(c,p,h,u,f,m){return i(),t("div",null,l)}const S=a(s,[["render",d]]);export{v as __pageData,S as default}; +import{_ as a,c as t,o as i,b as e,d as r}from"./chunks/framework.D4bY2S_W.js";const v=JSON.parse('{"title":"Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays","description":"","frontmatter":{"layout":"paper","title":"Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays","date":"2020-05-06","authors":["Katharine HD Crawford","Rachel Eguia","Adam S Dingens","Andrea N Loes","Keara D Malone","Caitlin R Wolf","Helen Y Chu","M Alejandra Tortorici","David Veesler","Michael Murphy","Deleah Pettie","Neil P King","Alejandro B Balazs","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12050513","link":"https://www.mdpi.com/1999-4915/12/5/513","image":"/assets/papers/2020_crawford.jpg","keywords":["SARS-CoV-2","Immunity","Pseudovirus"]},"headers":[],"relativePath":"papers/2020_crawford.md","filePath":"papers/2020_crawford.md"}'),s={name:"papers/2020_crawford.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"SARS-CoV-2 enters cells using its Spike protein, which is also the main target of neutralizing antibodies. Therefore, assays to measure how antibodies and sera affect Spike-mediated viral infection are important for studying immunity. Because SARS-CoV-2 is a biosafety-level-3 virus, one way to simplify such assays is to pseudotype biosafety-level-2 viral particles with Spike. Such pseudotyping has now been described for single-cycle lentiviral, retroviral, and vesicular stomatitis virus (VSV) particles, but the reagents and protocols are not widely available. Here, we detailed how to effectively pseudotype lentiviral particles with SARS-CoV-2 Spike and infect 293T cells engineered to express the SARS-CoV-2 receptor, ACE2. We also made all the key experimental reagents available in the BEI Resources repository of ATCC and the NIH. Furthermore, we demonstrated how these pseudotyped lentiviral particles could be used to measure the neutralizing activity of human sera or plasma against SARS-CoV-2 in convenient luciferase-based assays, thereby providing a valuable complement to ELISA-based methods that measure antibody binding rather than neutralization.",-1),l=[o,n];function d(c,p,h,u,f,m){return i(),t("div",null,l)}const S=a(s,[["render",d]]);export{v as __pageData,S as default}; diff --git a/assets/papers_2020_crawford.md.pF0wWDFV.lean.js b/assets/papers_2020_crawford.md.COKdMTcD.lean.js similarity index 97% rename from assets/papers_2020_crawford.md.pF0wWDFV.lean.js rename to assets/papers_2020_crawford.md.COKdMTcD.lean.js index 0e66812..9d575ce 100644 --- a/assets/papers_2020_crawford.md.pF0wWDFV.lean.js +++ b/assets/papers_2020_crawford.md.COKdMTcD.lean.js @@ -1 +1 @@ -import{_ as a,c as t,o as i,b as e,d as r}from"./chunks/framework.BqSDeblO.js";const v=JSON.parse('{"title":"Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays","description":"","frontmatter":{"layout":"paper","title":"Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays","date":"2020-05-06","authors":["Katharine HD Crawford","Rachel Eguia","Adam S Dingens","Andrea N Loes","Keara D Malone","Caitlin R Wolf","Helen Y Chu","M Alejandra Tortorici","David Veesler","Michael Murphy","Deleah Pettie","Neil P King","Alejandro B Balazs","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12050513","link":"https://www.mdpi.com/1999-4915/12/5/513","image":"/assets/papers/2020_crawford.jpg","keywords":["SARS-CoV-2","Immunity","Pseudovirus"]},"headers":[],"relativePath":"papers/2020_crawford.md","filePath":"papers/2020_crawford.md"}'),s={name:"papers/2020_crawford.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"SARS-CoV-2 enters cells using its Spike protein, which is also the main target of neutralizing antibodies. Therefore, assays to measure how antibodies and sera affect Spike-mediated viral infection are important for studying immunity. Because SARS-CoV-2 is a biosafety-level-3 virus, one way to simplify such assays is to pseudotype biosafety-level-2 viral particles with Spike. Such pseudotyping has now been described for single-cycle lentiviral, retroviral, and vesicular stomatitis virus (VSV) particles, but the reagents and protocols are not widely available. Here, we detailed how to effectively pseudotype lentiviral particles with SARS-CoV-2 Spike and infect 293T cells engineered to express the SARS-CoV-2 receptor, ACE2. We also made all the key experimental reagents available in the BEI Resources repository of ATCC and the NIH. Furthermore, we demonstrated how these pseudotyped lentiviral particles could be used to measure the neutralizing activity of human sera or plasma against SARS-CoV-2 in convenient luciferase-based assays, thereby providing a valuable complement to ELISA-based methods that measure antibody binding rather than neutralization.",-1),l=[o,n];function d(c,p,h,u,f,m){return i(),t("div",null,l)}const S=a(s,[["render",d]]);export{v as __pageData,S as default}; +import{_ as a,c as t,o as i,b as e,d as r}from"./chunks/framework.D4bY2S_W.js";const v=JSON.parse('{"title":"Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays","description":"","frontmatter":{"layout":"paper","title":"Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays","date":"2020-05-06","authors":["Katharine HD Crawford","Rachel Eguia","Adam S Dingens","Andrea N Loes","Keara D Malone","Caitlin R Wolf","Helen Y Chu","M Alejandra Tortorici","David Veesler","Michael Murphy","Deleah Pettie","Neil P King","Alejandro B Balazs","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12050513","link":"https://www.mdpi.com/1999-4915/12/5/513","image":"/assets/papers/2020_crawford.jpg","keywords":["SARS-CoV-2","Immunity","Pseudovirus"]},"headers":[],"relativePath":"papers/2020_crawford.md","filePath":"papers/2020_crawford.md"}'),s={name:"papers/2020_crawford.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"SARS-CoV-2 enters cells using its Spike protein, which is also the main target of neutralizing antibodies. Therefore, assays to measure how antibodies and sera affect Spike-mediated viral infection are important for studying immunity. Because SARS-CoV-2 is a biosafety-level-3 virus, one way to simplify such assays is to pseudotype biosafety-level-2 viral particles with Spike. Such pseudotyping has now been described for single-cycle lentiviral, retroviral, and vesicular stomatitis virus (VSV) particles, but the reagents and protocols are not widely available. Here, we detailed how to effectively pseudotype lentiviral particles with SARS-CoV-2 Spike and infect 293T cells engineered to express the SARS-CoV-2 receptor, ACE2. We also made all the key experimental reagents available in the BEI Resources repository of ATCC and the NIH. Furthermore, we demonstrated how these pseudotyped lentiviral particles could be used to measure the neutralizing activity of human sera or plasma against SARS-CoV-2 in convenient luciferase-based assays, thereby providing a valuable complement to ELISA-based methods that measure antibody binding rather than neutralization.",-1),l=[o,n];function d(c,p,h,u,f,m){return i(),t("div",null,l)}const S=a(s,[["render",d]]);export{v as __pageData,S as default}; diff --git a/assets/papers_2020_dingens.md.DuP2HjKC.js b/assets/papers_2020_dingens.md.bB3YILP3.js similarity index 97% rename from assets/papers_2020_dingens.md.DuP2HjKC.js rename to assets/papers_2020_dingens.md.bB3YILP3.js index 99d39b9..c023137 100644 --- a/assets/papers_2020_dingens.md.DuP2HjKC.js +++ b/assets/papers_2020_dingens.md.bB3YILP3.js @@ -1 +1 @@ -import{_ as i,c as t,o as a,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const S=JSON.parse('{"title":"Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak","description":"","frontmatter":{"layout":"paper","title":"Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak","date":"2020-09-01","authors":["Adam S Dingens","Katharine HD Crawford","Amanda Adler","Sarah L Steele","Kirsten Lacombe","Rachel Eguia","Fatima Amanat","Alexandra C Walls","Caitlin R Wolf","Michael Murphy","Deleah Pettie","Lauren Carter","Xuan Qin","Neil P King","David Veesler","Florian Krammer","Jane A Dickerson","Helen Y Chu","Janet A Englund","Jesse D Bloom"],"journal":"Nature communications","doi":"10.1038/s41467-020-18178-1","link":"https://www.nature.com/articles/s41467-020-18178-1","image":"/assets/papers/2020_dingens.jpg","keywords":["SARS-CoV-2","Pseudovirus","Immunity"]},"headers":[],"relativePath":"papers/2020_dingens.md","filePath":"papers/2020_dingens.md"}'),r={name:"papers/2020_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Children are strikingly underrepresented in COVID-19 case counts. In the United States, children represent 22% of the population but only 1.7% of confirmed SARS-CoV-2 cases as of April 2, 2020. One possibility is that symptom-based viral testing is less likely to identify infected children, since they often experience milder disease than adults. Here, to better assess the frequency of pediatric SARS-CoV-2 infection, we serologically screen 1,775 residual samples from Seattle Children’s Hospital collected from 1,076 children seeking medical care during March and April of 2020. Only one child was seropositive in March, but seven were seropositive in April for a period seroprevalence of ≈1%. Most seropositive children (6/8) were not suspected of having had COVID-19. The sera of seropositive children have neutralizing activity, including one that neutralized at a dilution > 1:18,000. Therefore, an increasing number of children seeking medical care were infected by SARS-CoV-2 during the early Seattle outbreak despite few positive viral tests.",-1),l=[s,o];function d(c,h,p,u,f,m){return a(),t("div",null,l)}const _=i(r,[["render",d]]);export{S as __pageData,_ as default}; +import{_ as i,c as t,o as a,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const S=JSON.parse('{"title":"Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak","description":"","frontmatter":{"layout":"paper","title":"Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak","date":"2020-09-01","authors":["Adam S Dingens","Katharine HD Crawford","Amanda Adler","Sarah L Steele","Kirsten Lacombe","Rachel Eguia","Fatima Amanat","Alexandra C Walls","Caitlin R Wolf","Michael Murphy","Deleah Pettie","Lauren Carter","Xuan Qin","Neil P King","David Veesler","Florian Krammer","Jane A Dickerson","Helen Y Chu","Janet A Englund","Jesse D Bloom"],"journal":"Nature communications","doi":"10.1038/s41467-020-18178-1","link":"https://www.nature.com/articles/s41467-020-18178-1","image":"/assets/papers/2020_dingens.jpg","keywords":["SARS-CoV-2","Pseudovirus","Immunity"]},"headers":[],"relativePath":"papers/2020_dingens.md","filePath":"papers/2020_dingens.md"}'),r={name:"papers/2020_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Children are strikingly underrepresented in COVID-19 case counts. In the United States, children represent 22% of the population but only 1.7% of confirmed SARS-CoV-2 cases as of April 2, 2020. One possibility is that symptom-based viral testing is less likely to identify infected children, since they often experience milder disease than adults. Here, to better assess the frequency of pediatric SARS-CoV-2 infection, we serologically screen 1,775 residual samples from Seattle Children’s Hospital collected from 1,076 children seeking medical care during March and April of 2020. Only one child was seropositive in March, but seven were seropositive in April for a period seroprevalence of ≈1%. Most seropositive children (6/8) were not suspected of having had COVID-19. The sera of seropositive children have neutralizing activity, including one that neutralized at a dilution > 1:18,000. Therefore, an increasing number of children seeking medical care were infected by SARS-CoV-2 during the early Seattle outbreak despite few positive viral tests.",-1),l=[s,o];function d(c,h,p,u,f,m){return a(),t("div",null,l)}const _=i(r,[["render",d]]);export{S as __pageData,_ as default}; diff --git a/assets/papers_2020_dingens.md.DuP2HjKC.lean.js b/assets/papers_2020_dingens.md.bB3YILP3.lean.js similarity index 97% rename from assets/papers_2020_dingens.md.DuP2HjKC.lean.js rename to assets/papers_2020_dingens.md.bB3YILP3.lean.js index 99d39b9..c023137 100644 --- a/assets/papers_2020_dingens.md.DuP2HjKC.lean.js +++ b/assets/papers_2020_dingens.md.bB3YILP3.lean.js @@ -1 +1 @@ -import{_ as i,c as t,o as a,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const S=JSON.parse('{"title":"Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak","description":"","frontmatter":{"layout":"paper","title":"Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak","date":"2020-09-01","authors":["Adam S Dingens","Katharine HD Crawford","Amanda Adler","Sarah L Steele","Kirsten Lacombe","Rachel Eguia","Fatima Amanat","Alexandra C Walls","Caitlin R Wolf","Michael Murphy","Deleah Pettie","Lauren Carter","Xuan Qin","Neil P King","David Veesler","Florian Krammer","Jane A Dickerson","Helen Y Chu","Janet A Englund","Jesse D Bloom"],"journal":"Nature communications","doi":"10.1038/s41467-020-18178-1","link":"https://www.nature.com/articles/s41467-020-18178-1","image":"/assets/papers/2020_dingens.jpg","keywords":["SARS-CoV-2","Pseudovirus","Immunity"]},"headers":[],"relativePath":"papers/2020_dingens.md","filePath":"papers/2020_dingens.md"}'),r={name:"papers/2020_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Children are strikingly underrepresented in COVID-19 case counts. In the United States, children represent 22% of the population but only 1.7% of confirmed SARS-CoV-2 cases as of April 2, 2020. One possibility is that symptom-based viral testing is less likely to identify infected children, since they often experience milder disease than adults. Here, to better assess the frequency of pediatric SARS-CoV-2 infection, we serologically screen 1,775 residual samples from Seattle Children’s Hospital collected from 1,076 children seeking medical care during March and April of 2020. Only one child was seropositive in March, but seven were seropositive in April for a period seroprevalence of ≈1%. Most seropositive children (6/8) were not suspected of having had COVID-19. The sera of seropositive children have neutralizing activity, including one that neutralized at a dilution > 1:18,000. Therefore, an increasing number of children seeking medical care were infected by SARS-CoV-2 during the early Seattle outbreak despite few positive viral tests.",-1),l=[s,o];function d(c,h,p,u,f,m){return a(),t("div",null,l)}const _=i(r,[["render",d]]);export{S as __pageData,_ as default}; +import{_ as i,c as t,o as a,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const S=JSON.parse('{"title":"Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak","description":"","frontmatter":{"layout":"paper","title":"Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak","date":"2020-09-01","authors":["Adam S Dingens","Katharine HD Crawford","Amanda Adler","Sarah L Steele","Kirsten Lacombe","Rachel Eguia","Fatima Amanat","Alexandra C Walls","Caitlin R Wolf","Michael Murphy","Deleah Pettie","Lauren Carter","Xuan Qin","Neil P King","David Veesler","Florian Krammer","Jane A Dickerson","Helen Y Chu","Janet A Englund","Jesse D Bloom"],"journal":"Nature communications","doi":"10.1038/s41467-020-18178-1","link":"https://www.nature.com/articles/s41467-020-18178-1","image":"/assets/papers/2020_dingens.jpg","keywords":["SARS-CoV-2","Pseudovirus","Immunity"]},"headers":[],"relativePath":"papers/2020_dingens.md","filePath":"papers/2020_dingens.md"}'),r={name:"papers/2020_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Children are strikingly underrepresented in COVID-19 case counts. In the United States, children represent 22% of the population but only 1.7% of confirmed SARS-CoV-2 cases as of April 2, 2020. One possibility is that symptom-based viral testing is less likely to identify infected children, since they often experience milder disease than adults. Here, to better assess the frequency of pediatric SARS-CoV-2 infection, we serologically screen 1,775 residual samples from Seattle Children’s Hospital collected from 1,076 children seeking medical care during March and April of 2020. Only one child was seropositive in March, but seven were seropositive in April for a period seroprevalence of ≈1%. Most seropositive children (6/8) were not suspected of having had COVID-19. The sera of seropositive children have neutralizing activity, including one that neutralized at a dilution > 1:18,000. Therefore, an increasing number of children seeking medical care were infected by SARS-CoV-2 during the early Seattle outbreak despite few positive viral tests.",-1),l=[s,o];function d(c,h,p,u,f,m){return a(),t("div",null,l)}const _=i(r,[["render",d]]);export{S as __pageData,_ as default}; diff --git a/assets/papers_2020_einav_b.md.vrVqpYWt.js b/assets/papers_2020_einav_b.md.Cf2gD3fe.js similarity index 96% rename from assets/papers_2020_einav_b.md.vrVqpYWt.js rename to assets/papers_2020_einav_b.md.Cf2gD3fe.js index 6dd72ef..0bf7826 100644 --- a/assets/papers_2020_einav_b.md.vrVqpYWt.js +++ b/assets/papers_2020_einav_b.md.Cf2gD3fe.js @@ -1 +1 @@ -import{_ as t,c as a,o as i,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"When two are better than one: Modeling the mechanisms of antibody mixtures","description":"","frontmatter":{"layout":"paper","title":"When two are better than one: Modeling the mechanisms of antibody mixtures","date":"2020-05-04","authors":["Tal Einav","Jesse D Bloom"],"journal":"PLoS computational biology","doi":"10.1371/journal.pcbi.1007830","link":"https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1007830","image":"/assets/papers/2020_einav_b.png","keywords":["Modeling","Immunity"]},"headers":[],"relativePath":"papers/2020_einav_b.md","filePath":"papers/2020_einav_b.md"}'),n={name:"papers/2020_einav_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"It is difficult to predict how antibodies will behave when mixed together, even after each has been independently characterized. Here, we present a statistical mechanical model for the activity of antibody mixtures that accounts for whether pairs of antibodies bind to distinct or overlapping epitopes. This model requires measuring n individual antibodies and their pairwise interactions to predict the 2n potential combinations. We apply this model to epidermal growth factor receptor (EGFR) antibodies and find that the activity of antibody mixtures can be predicted without positing synergy at the molecular level. In addition, we demonstrate how the model can be used in reverse, where straightforward experiments measuring the activity of antibody mixtures can be used to infer the molecular interactions between antibodies. Lastly, we generalize this model to analyze engineered multidomain antibodies, where components of different antibodies are tethered together to form novel amalgams, and characterize how well it predicts recently designed influenza antibodies.",-1),d=[r,s];function l(c,h,p,m,b,u){return i(),a("div",null,d)}const g=t(n,[["render",l]]);export{_ as __pageData,g as default}; +import{_ as t,c as a,o as i,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"When two are better than one: Modeling the mechanisms of antibody mixtures","description":"","frontmatter":{"layout":"paper","title":"When two are better than one: Modeling the mechanisms of antibody mixtures","date":"2020-05-04","authors":["Tal Einav","Jesse D Bloom"],"journal":"PLoS computational biology","doi":"10.1371/journal.pcbi.1007830","link":"https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1007830","image":"/assets/papers/2020_einav_b.png","keywords":["Modeling","Immunity"]},"headers":[],"relativePath":"papers/2020_einav_b.md","filePath":"papers/2020_einav_b.md"}'),n={name:"papers/2020_einav_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"It is difficult to predict how antibodies will behave when mixed together, even after each has been independently characterized. Here, we present a statistical mechanical model for the activity of antibody mixtures that accounts for whether pairs of antibodies bind to distinct or overlapping epitopes. This model requires measuring n individual antibodies and their pairwise interactions to predict the 2n potential combinations. We apply this model to epidermal growth factor receptor (EGFR) antibodies and find that the activity of antibody mixtures can be predicted without positing synergy at the molecular level. In addition, we demonstrate how the model can be used in reverse, where straightforward experiments measuring the activity of antibody mixtures can be used to infer the molecular interactions between antibodies. Lastly, we generalize this model to analyze engineered multidomain antibodies, where components of different antibodies are tethered together to form novel amalgams, and characterize how well it predicts recently designed influenza antibodies.",-1),d=[r,s];function l(c,h,p,m,b,u){return i(),a("div",null,d)}const g=t(n,[["render",l]]);export{_ as __pageData,g as default}; diff --git a/assets/papers_2020_einav_b.md.vrVqpYWt.lean.js b/assets/papers_2020_einav_b.md.Cf2gD3fe.lean.js similarity index 96% rename from assets/papers_2020_einav_b.md.vrVqpYWt.lean.js rename to assets/papers_2020_einav_b.md.Cf2gD3fe.lean.js index 6dd72ef..0bf7826 100644 --- a/assets/papers_2020_einav_b.md.vrVqpYWt.lean.js +++ b/assets/papers_2020_einav_b.md.Cf2gD3fe.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as i,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"When two are better than one: Modeling the mechanisms of antibody mixtures","description":"","frontmatter":{"layout":"paper","title":"When two are better than one: Modeling the mechanisms of antibody mixtures","date":"2020-05-04","authors":["Tal Einav","Jesse D Bloom"],"journal":"PLoS computational biology","doi":"10.1371/journal.pcbi.1007830","link":"https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1007830","image":"/assets/papers/2020_einav_b.png","keywords":["Modeling","Immunity"]},"headers":[],"relativePath":"papers/2020_einav_b.md","filePath":"papers/2020_einav_b.md"}'),n={name:"papers/2020_einav_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"It is difficult to predict how antibodies will behave when mixed together, even after each has been independently characterized. Here, we present a statistical mechanical model for the activity of antibody mixtures that accounts for whether pairs of antibodies bind to distinct or overlapping epitopes. This model requires measuring n individual antibodies and their pairwise interactions to predict the 2n potential combinations. We apply this model to epidermal growth factor receptor (EGFR) antibodies and find that the activity of antibody mixtures can be predicted without positing synergy at the molecular level. In addition, we demonstrate how the model can be used in reverse, where straightforward experiments measuring the activity of antibody mixtures can be used to infer the molecular interactions between antibodies. Lastly, we generalize this model to analyze engineered multidomain antibodies, where components of different antibodies are tethered together to form novel amalgams, and characterize how well it predicts recently designed influenza antibodies.",-1),d=[r,s];function l(c,h,p,m,b,u){return i(),a("div",null,d)}const g=t(n,[["render",l]]);export{_ as __pageData,g as default}; +import{_ as t,c as a,o as i,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"When two are better than one: Modeling the mechanisms of antibody mixtures","description":"","frontmatter":{"layout":"paper","title":"When two are better than one: Modeling the mechanisms of antibody mixtures","date":"2020-05-04","authors":["Tal Einav","Jesse D Bloom"],"journal":"PLoS computational biology","doi":"10.1371/journal.pcbi.1007830","link":"https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1007830","image":"/assets/papers/2020_einav_b.png","keywords":["Modeling","Immunity"]},"headers":[],"relativePath":"papers/2020_einav_b.md","filePath":"papers/2020_einav_b.md"}'),n={name:"papers/2020_einav_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"It is difficult to predict how antibodies will behave when mixed together, even after each has been independently characterized. Here, we present a statistical mechanical model for the activity of antibody mixtures that accounts for whether pairs of antibodies bind to distinct or overlapping epitopes. This model requires measuring n individual antibodies and their pairwise interactions to predict the 2n potential combinations. We apply this model to epidermal growth factor receptor (EGFR) antibodies and find that the activity of antibody mixtures can be predicted without positing synergy at the molecular level. In addition, we demonstrate how the model can be used in reverse, where straightforward experiments measuring the activity of antibody mixtures can be used to infer the molecular interactions between antibodies. Lastly, we generalize this model to analyze engineered multidomain antibodies, where components of different antibodies are tethered together to form novel amalgams, and characterize how well it predicts recently designed influenza antibodies.",-1),d=[r,s];function l(c,h,p,m,b,u){return i(),a("div",null,d)}const g=t(n,[["render",l]]);export{_ as __pageData,g as default}; diff --git a/assets/papers_2020_gentles.md.oFkQm2nP.js b/assets/papers_2020_gentles.md.CU4t53Mc.js similarity index 97% rename from assets/papers_2020_gentles.md.oFkQm2nP.js rename to assets/papers_2020_gentles.md.CU4t53Mc.js index dde621a..406c814 100644 --- a/assets/papers_2020_gentles.md.oFkQm2nP.js +++ b/assets/papers_2020_gentles.md.CU4t53Mc.js @@ -1 +1 @@ -import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.BqSDeblO.js";const m=JSON.parse('{"title":"Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding","description":"","frontmatter":{"layout":"paper","title":"Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding","date":"2020-05-30","authors":["Lauren E Gentles","Hongquan Wan","Maryna C Eichelberger","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12060597","link":"https://www.mdpi.com/1999-4915/12/6/597","image":"/assets/papers/2020_gentles.png","keywords":["Influenza"]},"headers":[],"relativePath":"papers/2020_gentles.md","filePath":"papers/2020_gentles.md"}'),s={name:"papers/2020_gentles.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza virus infection elicits antibodies against the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Because HA is essential for viral entry, antibodies targeting HA often potently neutralize the virus in single-cycle infection assays. However, antibodies against NA are not potently neutralizing in such assays, since NA is dispensable for single-cycle infection. Here we show that a modified influenza virus that depends on NA for receptor binding is much more sensitive than a virus with receptor-binding HA to neutralization by some anti-NA antibodies. Specifically, a virus with a receptor-binding G147R N1 NA and a binding-deficient HA is completely neutralized in single-cycle infections by an antibody that binds near the NA active site. Infection is also substantially inhibited by antibodies that bind NA epitopes distant from the active site. Finally, we demonstrate that this modified virus can be used to efficiently select mutations in NA that escape antibody binding, a task that can be laborious with typical influenza viruses that are not well neutralized by anti-NA antibodies. Thus, viruses dependent on NA for receptor binding allow for sensitive in vitro detection of antibodies binding near the catalytic site of NA and enable the selection of viral escape mutants.",-1),l=[o,r];function c(d,u,p,b,h,f){return n(),i("div",null,l)}const y=t(s,[["render",c]]);export{m as __pageData,y as default}; +import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.D4bY2S_W.js";const m=JSON.parse('{"title":"Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding","description":"","frontmatter":{"layout":"paper","title":"Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding","date":"2020-05-30","authors":["Lauren E Gentles","Hongquan Wan","Maryna C Eichelberger","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12060597","link":"https://www.mdpi.com/1999-4915/12/6/597","image":"/assets/papers/2020_gentles.png","keywords":["Influenza"]},"headers":[],"relativePath":"papers/2020_gentles.md","filePath":"papers/2020_gentles.md"}'),s={name:"papers/2020_gentles.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza virus infection elicits antibodies against the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Because HA is essential for viral entry, antibodies targeting HA often potently neutralize the virus in single-cycle infection assays. However, antibodies against NA are not potently neutralizing in such assays, since NA is dispensable for single-cycle infection. Here we show that a modified influenza virus that depends on NA for receptor binding is much more sensitive than a virus with receptor-binding HA to neutralization by some anti-NA antibodies. Specifically, a virus with a receptor-binding G147R N1 NA and a binding-deficient HA is completely neutralized in single-cycle infections by an antibody that binds near the NA active site. Infection is also substantially inhibited by antibodies that bind NA epitopes distant from the active site. Finally, we demonstrate that this modified virus can be used to efficiently select mutations in NA that escape antibody binding, a task that can be laborious with typical influenza viruses that are not well neutralized by anti-NA antibodies. Thus, viruses dependent on NA for receptor binding allow for sensitive in vitro detection of antibodies binding near the catalytic site of NA and enable the selection of viral escape mutants.",-1),l=[o,r];function c(d,u,p,b,h,f){return n(),i("div",null,l)}const y=t(s,[["render",c]]);export{m as __pageData,y as default}; diff --git a/assets/papers_2020_gentles.md.oFkQm2nP.lean.js b/assets/papers_2020_gentles.md.CU4t53Mc.lean.js similarity index 97% rename from assets/papers_2020_gentles.md.oFkQm2nP.lean.js rename to assets/papers_2020_gentles.md.CU4t53Mc.lean.js index dde621a..406c814 100644 --- a/assets/papers_2020_gentles.md.oFkQm2nP.lean.js +++ b/assets/papers_2020_gentles.md.CU4t53Mc.lean.js @@ -1 +1 @@ -import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.BqSDeblO.js";const m=JSON.parse('{"title":"Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding","description":"","frontmatter":{"layout":"paper","title":"Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding","date":"2020-05-30","authors":["Lauren E Gentles","Hongquan Wan","Maryna C Eichelberger","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12060597","link":"https://www.mdpi.com/1999-4915/12/6/597","image":"/assets/papers/2020_gentles.png","keywords":["Influenza"]},"headers":[],"relativePath":"papers/2020_gentles.md","filePath":"papers/2020_gentles.md"}'),s={name:"papers/2020_gentles.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza virus infection elicits antibodies against the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Because HA is essential for viral entry, antibodies targeting HA often potently neutralize the virus in single-cycle infection assays. However, antibodies against NA are not potently neutralizing in such assays, since NA is dispensable for single-cycle infection. Here we show that a modified influenza virus that depends on NA for receptor binding is much more sensitive than a virus with receptor-binding HA to neutralization by some anti-NA antibodies. Specifically, a virus with a receptor-binding G147R N1 NA and a binding-deficient HA is completely neutralized in single-cycle infections by an antibody that binds near the NA active site. Infection is also substantially inhibited by antibodies that bind NA epitopes distant from the active site. Finally, we demonstrate that this modified virus can be used to efficiently select mutations in NA that escape antibody binding, a task that can be laborious with typical influenza viruses that are not well neutralized by anti-NA antibodies. Thus, viruses dependent on NA for receptor binding allow for sensitive in vitro detection of antibodies binding near the catalytic site of NA and enable the selection of viral escape mutants.",-1),l=[o,r];function c(d,u,p,b,h,f){return n(),i("div",null,l)}const y=t(s,[["render",c]]);export{m as __pageData,y as default}; +import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.D4bY2S_W.js";const m=JSON.parse('{"title":"Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding","description":"","frontmatter":{"layout":"paper","title":"Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding","date":"2020-05-30","authors":["Lauren E Gentles","Hongquan Wan","Maryna C Eichelberger","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12060597","link":"https://www.mdpi.com/1999-4915/12/6/597","image":"/assets/papers/2020_gentles.png","keywords":["Influenza"]},"headers":[],"relativePath":"papers/2020_gentles.md","filePath":"papers/2020_gentles.md"}'),s={name:"papers/2020_gentles.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza virus infection elicits antibodies against the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Because HA is essential for viral entry, antibodies targeting HA often potently neutralize the virus in single-cycle infection assays. However, antibodies against NA are not potently neutralizing in such assays, since NA is dispensable for single-cycle infection. Here we show that a modified influenza virus that depends on NA for receptor binding is much more sensitive than a virus with receptor-binding HA to neutralization by some anti-NA antibodies. Specifically, a virus with a receptor-binding G147R N1 NA and a binding-deficient HA is completely neutralized in single-cycle infections by an antibody that binds near the NA active site. Infection is also substantially inhibited by antibodies that bind NA epitopes distant from the active site. Finally, we demonstrate that this modified virus can be used to efficiently select mutations in NA that escape antibody binding, a task that can be laborious with typical influenza viruses that are not well neutralized by anti-NA antibodies. Thus, viruses dependent on NA for receptor binding allow for sensitive in vitro detection of antibodies binding near the catalytic site of NA and enable the selection of viral escape mutants.",-1),l=[o,r];function c(d,u,p,b,h,f){return n(),i("div",null,l)}const y=t(s,[["render",c]]);export{m as __pageData,y as default}; diff --git a/assets/papers_2020_hilton.md.ePlGR8tB.js b/assets/papers_2020_hilton.md.Dq9V-1yM.js similarity index 95% rename from assets/papers_2020_hilton.md.ePlGR8tB.js rename to assets/papers_2020_hilton.md.Dq9V-1yM.js index bd50846..a1478e1 100644 --- a/assets/papers_2020_hilton.md.ePlGR8tB.js +++ b/assets/papers_2020_hilton.md.Dq9V-1yM.js @@ -1 +1 @@ -import{_ as a,c as o,o as s,b as e,d as t}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"dms-view: Interactive visualization tool for deep mutational scanning data","description":"","frontmatter":{"layout":"paper","title":"dms-view: Interactive visualization tool for deep mutational scanning data","date":"2020-08-17","authors":["Sarah K Hilton*","John Huddleston*","Allison Black","Khrystyna North","Adam S Dingens","Trevor Bedford","Jesse D Bloom"],"journal":"JOSS","doi":"10.21105/joss.02353","link":"https://joss.theoj.org/papers/10.21105/joss.02353","image":"/assets/papers/2020_hilton.png","keywords":["Deep mutational scanning","Software tools"]},"headers":[],"relativePath":"papers/2020_hilton.md","filePath":"papers/2020_hilton.md"}'),r={name:"papers/2020_hilton.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,[t("Here we describe dms-view ("),e("a",{href:"https://dms-view.github.io/",target:"_blank",rel:"noreferrer"},"https://dms-view.github.io/"),t("), a flexible, web-based, interactive visualization tool for DMS data.")],-1),l=[i,n];function d(c,p,h,_,m,u){return s(),o("div",null,l)}const v=a(r,[["render",d]]);export{b as __pageData,v as default}; +import{_ as a,c as o,o as s,b as e,d as t}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"dms-view: Interactive visualization tool for deep mutational scanning data","description":"","frontmatter":{"layout":"paper","title":"dms-view: Interactive visualization tool for deep mutational scanning data","date":"2020-08-17","authors":["Sarah K Hilton*","John Huddleston*","Allison Black","Khrystyna North","Adam S Dingens","Trevor Bedford","Jesse D Bloom"],"journal":"JOSS","doi":"10.21105/joss.02353","link":"https://joss.theoj.org/papers/10.21105/joss.02353","image":"/assets/papers/2020_hilton.png","keywords":["Deep mutational scanning","Software tools"]},"headers":[],"relativePath":"papers/2020_hilton.md","filePath":"papers/2020_hilton.md"}'),r={name:"papers/2020_hilton.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,[t("Here we describe dms-view ("),e("a",{href:"https://dms-view.github.io/",target:"_blank",rel:"noreferrer"},"https://dms-view.github.io/"),t("), a flexible, web-based, interactive visualization tool for DMS data.")],-1),l=[i,n];function d(c,p,h,_,m,u){return s(),o("div",null,l)}const v=a(r,[["render",d]]);export{b as __pageData,v as default}; diff --git a/assets/papers_2020_hilton.md.ePlGR8tB.lean.js b/assets/papers_2020_hilton.md.Dq9V-1yM.lean.js similarity index 95% rename from assets/papers_2020_hilton.md.ePlGR8tB.lean.js rename to assets/papers_2020_hilton.md.Dq9V-1yM.lean.js index bd50846..a1478e1 100644 --- a/assets/papers_2020_hilton.md.ePlGR8tB.lean.js +++ b/assets/papers_2020_hilton.md.Dq9V-1yM.lean.js @@ -1 +1 @@ -import{_ as a,c as o,o as s,b as e,d as t}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"dms-view: Interactive visualization tool for deep mutational scanning data","description":"","frontmatter":{"layout":"paper","title":"dms-view: Interactive visualization tool for deep mutational scanning data","date":"2020-08-17","authors":["Sarah K Hilton*","John Huddleston*","Allison Black","Khrystyna North","Adam S Dingens","Trevor Bedford","Jesse D Bloom"],"journal":"JOSS","doi":"10.21105/joss.02353","link":"https://joss.theoj.org/papers/10.21105/joss.02353","image":"/assets/papers/2020_hilton.png","keywords":["Deep mutational scanning","Software tools"]},"headers":[],"relativePath":"papers/2020_hilton.md","filePath":"papers/2020_hilton.md"}'),r={name:"papers/2020_hilton.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,[t("Here we describe dms-view ("),e("a",{href:"https://dms-view.github.io/",target:"_blank",rel:"noreferrer"},"https://dms-view.github.io/"),t("), a flexible, web-based, interactive visualization tool for DMS data.")],-1),l=[i,n];function d(c,p,h,_,m,u){return s(),o("div",null,l)}const v=a(r,[["render",d]]);export{b as __pageData,v as default}; +import{_ as a,c as o,o as s,b as e,d as t}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"dms-view: Interactive visualization tool for deep mutational scanning data","description":"","frontmatter":{"layout":"paper","title":"dms-view: Interactive visualization tool for deep mutational scanning data","date":"2020-08-17","authors":["Sarah K Hilton*","John Huddleston*","Allison Black","Khrystyna North","Adam S Dingens","Trevor Bedford","Jesse D Bloom"],"journal":"JOSS","doi":"10.21105/joss.02353","link":"https://joss.theoj.org/papers/10.21105/joss.02353","image":"/assets/papers/2020_hilton.png","keywords":["Deep mutational scanning","Software tools"]},"headers":[],"relativePath":"papers/2020_hilton.md","filePath":"papers/2020_hilton.md"}'),r={name:"papers/2020_hilton.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,[t("Here we describe dms-view ("),e("a",{href:"https://dms-view.github.io/",target:"_blank",rel:"noreferrer"},"https://dms-view.github.io/"),t("), a flexible, web-based, interactive visualization tool for DMS data.")],-1),l=[i,n];function d(c,p,h,_,m,u){return s(),o("div",null,l)}const v=a(r,[["render",d]]);export{b as __pageData,v as default}; diff --git a/assets/papers_2020_loes.md.B058llpp.js b/assets/papers_2020_loes.md.CmmoyyvP.js similarity index 96% rename from assets/papers_2020_loes.md.B058llpp.js rename to assets/papers_2020_loes.md.CmmoyyvP.js index 570e647..55f274b 100644 --- a/assets/papers_2020_loes.md.B058llpp.js +++ b/assets/papers_2020_loes.md.CmmoyyvP.js @@ -1 +1 @@ -import{_ as i,c as a,o as n,b as e,d as t}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice","description":"","frontmatter":{"layout":"paper","title":"Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice","date":"2020-09-05","authors":["Andrea N Loes","Lauren E Gentles","Allison J Greaney","Katharine HD Crawford","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12090987","link":"https://www.mdpi.com/1999-4915/12/9/987","image":"/assets/papers/2020_loes.jpg","keywords":["SARS-CoV-2","Influenza","Vaccines"]},"headers":[],"relativePath":"papers/2020_loes.md","filePath":"papers/2020_loes.md"}'),s={name:"papers/2020_loes.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"An effective vaccine is essential for controlling the spread of the SARS-CoV-2 virus. Here, we describe an influenza virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ΔNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ΔNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (~1:200). Furthermore, ΔNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ΔNA(RBD)-Flu at scale by leveraging existing platforms for the production of influenza vaccines.",-1),c=[o,r];function l(d,u,p,f,m,h){return n(),a("div",null,c)}const _=i(s,[["render",l]]);export{b as __pageData,_ as default}; +import{_ as i,c as a,o as n,b as e,d as t}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice","description":"","frontmatter":{"layout":"paper","title":"Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice","date":"2020-09-05","authors":["Andrea N Loes","Lauren E Gentles","Allison J Greaney","Katharine HD Crawford","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12090987","link":"https://www.mdpi.com/1999-4915/12/9/987","image":"/assets/papers/2020_loes.jpg","keywords":["SARS-CoV-2","Influenza","Vaccines"]},"headers":[],"relativePath":"papers/2020_loes.md","filePath":"papers/2020_loes.md"}'),s={name:"papers/2020_loes.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"An effective vaccine is essential for controlling the spread of the SARS-CoV-2 virus. Here, we describe an influenza virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ΔNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ΔNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (~1:200). Furthermore, ΔNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ΔNA(RBD)-Flu at scale by leveraging existing platforms for the production of influenza vaccines.",-1),c=[o,r];function l(d,u,p,f,m,h){return n(),a("div",null,c)}const _=i(s,[["render",l]]);export{b as __pageData,_ as default}; diff --git a/assets/papers_2020_loes.md.B058llpp.lean.js b/assets/papers_2020_loes.md.CmmoyyvP.lean.js similarity index 96% rename from assets/papers_2020_loes.md.B058llpp.lean.js rename to assets/papers_2020_loes.md.CmmoyyvP.lean.js index 570e647..55f274b 100644 --- a/assets/papers_2020_loes.md.B058llpp.lean.js +++ b/assets/papers_2020_loes.md.CmmoyyvP.lean.js @@ -1 +1 @@ -import{_ as i,c as a,o as n,b as e,d as t}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice","description":"","frontmatter":{"layout":"paper","title":"Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice","date":"2020-09-05","authors":["Andrea N Loes","Lauren E Gentles","Allison J Greaney","Katharine HD Crawford","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12090987","link":"https://www.mdpi.com/1999-4915/12/9/987","image":"/assets/papers/2020_loes.jpg","keywords":["SARS-CoV-2","Influenza","Vaccines"]},"headers":[],"relativePath":"papers/2020_loes.md","filePath":"papers/2020_loes.md"}'),s={name:"papers/2020_loes.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"An effective vaccine is essential for controlling the spread of the SARS-CoV-2 virus. Here, we describe an influenza virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ΔNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ΔNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (~1:200). Furthermore, ΔNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ΔNA(RBD)-Flu at scale by leveraging existing platforms for the production of influenza vaccines.",-1),c=[o,r];function l(d,u,p,f,m,h){return n(),a("div",null,c)}const _=i(s,[["render",l]]);export{b as __pageData,_ as default}; +import{_ as i,c as a,o as n,b as e,d as t}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice","description":"","frontmatter":{"layout":"paper","title":"Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice","date":"2020-09-05","authors":["Andrea N Loes","Lauren E Gentles","Allison J Greaney","Katharine HD Crawford","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12090987","link":"https://www.mdpi.com/1999-4915/12/9/987","image":"/assets/papers/2020_loes.jpg","keywords":["SARS-CoV-2","Influenza","Vaccines"]},"headers":[],"relativePath":"papers/2020_loes.md","filePath":"papers/2020_loes.md"}'),s={name:"papers/2020_loes.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"An effective vaccine is essential for controlling the spread of the SARS-CoV-2 virus. Here, we describe an influenza virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ΔNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ΔNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (~1:200). Furthermore, ΔNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ΔNA(RBD)-Flu at scale by leveraging existing platforms for the production of influenza vaccines.",-1),c=[o,r];function l(d,u,p,f,m,h){return n(),a("div",null,c)}const _=i(s,[["render",l]]);export{b as __pageData,_ as default}; diff --git a/assets/papers_2020_roop.md.DtDpJBds.js b/assets/papers_2020_roop.md.BpQAw3YD.js similarity index 97% rename from assets/papers_2020_roop.md.DtDpJBds.js rename to assets/papers_2020_roop.md.BpQAw3YD.js index 8f66339..eaa0838 100644 --- a/assets/papers_2020_roop.md.DtDpJBds.js +++ b/assets/papers_2020_roop.md.BpQAw3YD.js @@ -1 +1 @@ -import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const y=JSON.parse('{"title":"Identification of HIV-1 envelope mutations that enhance entry using macaque CD4 and CCR5","description":"","frontmatter":{"layout":"paper","title":"Identification of HIV-1 envelope mutations that enhance entry using macaque CD4 and CCR5","date":"2020-02-21","authors":["Jeremy I Roop","Noah A Cassidy","Adam S Dingens","Jesse D Bloom","Julie Overbaugh"],"journal":"Viruses","doi":"10.3390/v12020241","link":"https://www.mdpi.com/1999-4915/12/2/241","image":"/assets/papers/2020_roop.jpg","keywords":["HIV"]},"headers":[],"relativePath":"papers/2020_roop.md","filePath":"papers/2020_roop.md"}'),i={name:"papers/2020_roop.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Although Rhesus macaques are an important animal model for HIV-1 vaccine development research, most transmitted HIV-1 strains replicate poorly in macaque cells. A major genetic determinant of this species-specific restriction is a non-synonymous mutation in macaque CD4 that results in reduced HIV-1 Envelope (Env)-mediated viral entry compared to human CD4. Recent research efforts employing either laboratory evolution or structure-guided design strategies have uncovered several mutations in Env’s gp120 subunit that enhance binding of macaque CD4 by transmitted/founder HIV-1 viruses. In order to identify additional Env mutations that promote infection of macaque cells, we utilized deep mutational scanning to screen thousands of Env point mutants for those that enhance HIV-1 entry via macaque receptors. We identified many uncharacterized amino acid mutations in the N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR) regions of gp41 that increased entry into cells bearing macaque receptors up to 9-fold. Many of these mutations also modestly increased infection of cells bearing human CD4 and CCR5 (up to 1.5-fold). NHR/CHR mutations identified by deep mutational scanning that enhanced entry also increased sensitivity to neutralizing antibodies targeting the MPER epitope, and to inactivation by cold-incubation, suggesting that they promote sampling of an intermediate trimer conformation between closed and receptor bound states. Identification of this set of mutations can inform future macaque model studies, and also further our understanding of the relationship between Env structure and function.",-1),c=[s,r];function d(u,m,l,p,h,f){return n(),a("div",null,c)}const v=t(i,[["render",d]]);export{y as __pageData,v as default}; +import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const y=JSON.parse('{"title":"Identification of HIV-1 envelope mutations that enhance entry using macaque CD4 and CCR5","description":"","frontmatter":{"layout":"paper","title":"Identification of HIV-1 envelope mutations that enhance entry using macaque CD4 and CCR5","date":"2020-02-21","authors":["Jeremy I Roop","Noah A Cassidy","Adam S Dingens","Jesse D Bloom","Julie Overbaugh"],"journal":"Viruses","doi":"10.3390/v12020241","link":"https://www.mdpi.com/1999-4915/12/2/241","image":"/assets/papers/2020_roop.jpg","keywords":["HIV"]},"headers":[],"relativePath":"papers/2020_roop.md","filePath":"papers/2020_roop.md"}'),i={name:"papers/2020_roop.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Although Rhesus macaques are an important animal model for HIV-1 vaccine development research, most transmitted HIV-1 strains replicate poorly in macaque cells. A major genetic determinant of this species-specific restriction is a non-synonymous mutation in macaque CD4 that results in reduced HIV-1 Envelope (Env)-mediated viral entry compared to human CD4. Recent research efforts employing either laboratory evolution or structure-guided design strategies have uncovered several mutations in Env’s gp120 subunit that enhance binding of macaque CD4 by transmitted/founder HIV-1 viruses. In order to identify additional Env mutations that promote infection of macaque cells, we utilized deep mutational scanning to screen thousands of Env point mutants for those that enhance HIV-1 entry via macaque receptors. We identified many uncharacterized amino acid mutations in the N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR) regions of gp41 that increased entry into cells bearing macaque receptors up to 9-fold. Many of these mutations also modestly increased infection of cells bearing human CD4 and CCR5 (up to 1.5-fold). NHR/CHR mutations identified by deep mutational scanning that enhanced entry also increased sensitivity to neutralizing antibodies targeting the MPER epitope, and to inactivation by cold-incubation, suggesting that they promote sampling of an intermediate trimer conformation between closed and receptor bound states. Identification of this set of mutations can inform future macaque model studies, and also further our understanding of the relationship between Env structure and function.",-1),c=[s,r];function d(u,m,l,p,h,f){return n(),a("div",null,c)}const v=t(i,[["render",d]]);export{y as __pageData,v as default}; diff --git a/assets/papers_2020_roop.md.DtDpJBds.lean.js b/assets/papers_2020_roop.md.BpQAw3YD.lean.js similarity index 97% rename from assets/papers_2020_roop.md.DtDpJBds.lean.js rename to assets/papers_2020_roop.md.BpQAw3YD.lean.js index 8f66339..eaa0838 100644 --- a/assets/papers_2020_roop.md.DtDpJBds.lean.js +++ b/assets/papers_2020_roop.md.BpQAw3YD.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const y=JSON.parse('{"title":"Identification of HIV-1 envelope mutations that enhance entry using macaque CD4 and CCR5","description":"","frontmatter":{"layout":"paper","title":"Identification of HIV-1 envelope mutations that enhance entry using macaque CD4 and CCR5","date":"2020-02-21","authors":["Jeremy I Roop","Noah A Cassidy","Adam S Dingens","Jesse D Bloom","Julie Overbaugh"],"journal":"Viruses","doi":"10.3390/v12020241","link":"https://www.mdpi.com/1999-4915/12/2/241","image":"/assets/papers/2020_roop.jpg","keywords":["HIV"]},"headers":[],"relativePath":"papers/2020_roop.md","filePath":"papers/2020_roop.md"}'),i={name:"papers/2020_roop.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Although Rhesus macaques are an important animal model for HIV-1 vaccine development research, most transmitted HIV-1 strains replicate poorly in macaque cells. A major genetic determinant of this species-specific restriction is a non-synonymous mutation in macaque CD4 that results in reduced HIV-1 Envelope (Env)-mediated viral entry compared to human CD4. Recent research efforts employing either laboratory evolution or structure-guided design strategies have uncovered several mutations in Env’s gp120 subunit that enhance binding of macaque CD4 by transmitted/founder HIV-1 viruses. In order to identify additional Env mutations that promote infection of macaque cells, we utilized deep mutational scanning to screen thousands of Env point mutants for those that enhance HIV-1 entry via macaque receptors. We identified many uncharacterized amino acid mutations in the N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR) regions of gp41 that increased entry into cells bearing macaque receptors up to 9-fold. Many of these mutations also modestly increased infection of cells bearing human CD4 and CCR5 (up to 1.5-fold). NHR/CHR mutations identified by deep mutational scanning that enhanced entry also increased sensitivity to neutralizing antibodies targeting the MPER epitope, and to inactivation by cold-incubation, suggesting that they promote sampling of an intermediate trimer conformation between closed and receptor bound states. Identification of this set of mutations can inform future macaque model studies, and also further our understanding of the relationship between Env structure and function.",-1),c=[s,r];function d(u,m,l,p,h,f){return n(),a("div",null,c)}const v=t(i,[["render",d]]);export{y as __pageData,v as default}; +import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const y=JSON.parse('{"title":"Identification of HIV-1 envelope mutations that enhance entry using macaque CD4 and CCR5","description":"","frontmatter":{"layout":"paper","title":"Identification of HIV-1 envelope mutations that enhance entry using macaque CD4 and CCR5","date":"2020-02-21","authors":["Jeremy I Roop","Noah A Cassidy","Adam S Dingens","Jesse D Bloom","Julie Overbaugh"],"journal":"Viruses","doi":"10.3390/v12020241","link":"https://www.mdpi.com/1999-4915/12/2/241","image":"/assets/papers/2020_roop.jpg","keywords":["HIV"]},"headers":[],"relativePath":"papers/2020_roop.md","filePath":"papers/2020_roop.md"}'),i={name:"papers/2020_roop.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Although Rhesus macaques are an important animal model for HIV-1 vaccine development research, most transmitted HIV-1 strains replicate poorly in macaque cells. A major genetic determinant of this species-specific restriction is a non-synonymous mutation in macaque CD4 that results in reduced HIV-1 Envelope (Env)-mediated viral entry compared to human CD4. Recent research efforts employing either laboratory evolution or structure-guided design strategies have uncovered several mutations in Env’s gp120 subunit that enhance binding of macaque CD4 by transmitted/founder HIV-1 viruses. In order to identify additional Env mutations that promote infection of macaque cells, we utilized deep mutational scanning to screen thousands of Env point mutants for those that enhance HIV-1 entry via macaque receptors. We identified many uncharacterized amino acid mutations in the N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR) regions of gp41 that increased entry into cells bearing macaque receptors up to 9-fold. Many of these mutations also modestly increased infection of cells bearing human CD4 and CCR5 (up to 1.5-fold). NHR/CHR mutations identified by deep mutational scanning that enhanced entry also increased sensitivity to neutralizing antibodies targeting the MPER epitope, and to inactivation by cold-incubation, suggesting that they promote sampling of an intermediate trimer conformation between closed and receptor bound states. Identification of this set of mutations can inform future macaque model studies, and also further our understanding of the relationship between Env structure and function.",-1),c=[s,r];function d(u,m,l,p,h,f){return n(),a("div",null,c)}const v=t(i,[["render",d]]);export{y as __pageData,v as default}; diff --git a/assets/papers_2020_starr_a.md.DiYEr5PP.js b/assets/papers_2020_starr_a.md.Cjc4mid6.js similarity index 97% rename from assets/papers_2020_starr_a.md.DiYEr5PP.js rename to assets/papers_2020_starr_a.md.Cjc4mid6.js index ea20066..922d419 100644 --- a/assets/papers_2020_starr_a.md.DiYEr5PP.js +++ b/assets/papers_2020_starr_a.md.Cjc4mid6.js @@ -1 +1 @@ -import{_ as a,c as n,o as t,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding","date":"2020-09-03","authors":["Tyler N Starr*","Allison J Greaney*","Sarah K Hilton","Daniel Ellis","Katharine HD Crawford","Adam S Dingens","Mary Jane Navarro","John E Bowen","Alejandra M Tortorici","Alexandra C Walls","Neil P King","David Veesler","Jesse D Bloom"],"journal":"Cell","doi":"10.1016/j.cell.2020.08.012","link":"https://www.sciencedirect.com/science/article/pii/S0092867420310035?via%3Dihub","image":"/assets/papers/2020_starr_a.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2020_starr_a.md","filePath":"papers/2020_starr_a.md"}'),r={name:"papers/2020_starr_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein mediates viral attachment to ACE2 receptor and is a major determinant of host range and a dominant target of neutralizing antibodies. Here, we experimentally measure how all amino acid mutations to the RBD affect expression of folded protein and its affinity for ACE2. Most mutations are deleterious for RBD expression and ACE2 binding, and we identify constrained regions on the RBD’s surface that may be desirable targets for vaccines and antibody-based therapeutics. But a substantial number of mutations are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses. However, we find no evidence that these ACE2-affinity-enhancing mutations have been selected in current SARS-CoV-2 pandemic isolates. We present an interactive visualization and open analysis pipeline to facilitate use of our dataset for vaccine design and functional annotation of mutations observed during viral surveillance.",-1),d=[o,s];function l(c,p,f,m,u,h){return t(),n("div",null,d)}const b=a(r,[["render",l]]);export{g as __pageData,b as default}; +import{_ as a,c as n,o as t,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding","date":"2020-09-03","authors":["Tyler N Starr*","Allison J Greaney*","Sarah K Hilton","Daniel Ellis","Katharine HD Crawford","Adam S Dingens","Mary Jane Navarro","John E Bowen","Alejandra M Tortorici","Alexandra C Walls","Neil P King","David Veesler","Jesse D Bloom"],"journal":"Cell","doi":"10.1016/j.cell.2020.08.012","link":"https://www.sciencedirect.com/science/article/pii/S0092867420310035?via%3Dihub","image":"/assets/papers/2020_starr_a.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2020_starr_a.md","filePath":"papers/2020_starr_a.md"}'),r={name:"papers/2020_starr_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein mediates viral attachment to ACE2 receptor and is a major determinant of host range and a dominant target of neutralizing antibodies. Here, we experimentally measure how all amino acid mutations to the RBD affect expression of folded protein and its affinity for ACE2. Most mutations are deleterious for RBD expression and ACE2 binding, and we identify constrained regions on the RBD’s surface that may be desirable targets for vaccines and antibody-based therapeutics. But a substantial number of mutations are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses. However, we find no evidence that these ACE2-affinity-enhancing mutations have been selected in current SARS-CoV-2 pandemic isolates. We present an interactive visualization and open analysis pipeline to facilitate use of our dataset for vaccine design and functional annotation of mutations observed during viral surveillance.",-1),d=[o,s];function l(c,p,f,m,u,h){return t(),n("div",null,d)}const b=a(r,[["render",l]]);export{g as __pageData,b as default}; diff --git a/assets/papers_2020_starr_a.md.DiYEr5PP.lean.js b/assets/papers_2020_starr_a.md.Cjc4mid6.lean.js similarity index 97% rename from assets/papers_2020_starr_a.md.DiYEr5PP.lean.js rename to assets/papers_2020_starr_a.md.Cjc4mid6.lean.js index ea20066..922d419 100644 --- a/assets/papers_2020_starr_a.md.DiYEr5PP.lean.js +++ b/assets/papers_2020_starr_a.md.Cjc4mid6.lean.js @@ -1 +1 @@ -import{_ as a,c as n,o as t,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding","date":"2020-09-03","authors":["Tyler N Starr*","Allison J Greaney*","Sarah K Hilton","Daniel Ellis","Katharine HD Crawford","Adam S Dingens","Mary Jane Navarro","John E Bowen","Alejandra M Tortorici","Alexandra C Walls","Neil P King","David Veesler","Jesse D Bloom"],"journal":"Cell","doi":"10.1016/j.cell.2020.08.012","link":"https://www.sciencedirect.com/science/article/pii/S0092867420310035?via%3Dihub","image":"/assets/papers/2020_starr_a.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2020_starr_a.md","filePath":"papers/2020_starr_a.md"}'),r={name:"papers/2020_starr_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein mediates viral attachment to ACE2 receptor and is a major determinant of host range and a dominant target of neutralizing antibodies. Here, we experimentally measure how all amino acid mutations to the RBD affect expression of folded protein and its affinity for ACE2. Most mutations are deleterious for RBD expression and ACE2 binding, and we identify constrained regions on the RBD’s surface that may be desirable targets for vaccines and antibody-based therapeutics. But a substantial number of mutations are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses. However, we find no evidence that these ACE2-affinity-enhancing mutations have been selected in current SARS-CoV-2 pandemic isolates. We present an interactive visualization and open analysis pipeline to facilitate use of our dataset for vaccine design and functional annotation of mutations observed during viral surveillance.",-1),d=[o,s];function l(c,p,f,m,u,h){return t(),n("div",null,d)}const b=a(r,[["render",l]]);export{g as __pageData,b as default}; +import{_ as a,c as n,o as t,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding","date":"2020-09-03","authors":["Tyler N Starr*","Allison J Greaney*","Sarah K Hilton","Daniel Ellis","Katharine HD Crawford","Adam S Dingens","Mary Jane Navarro","John E Bowen","Alejandra M Tortorici","Alexandra C Walls","Neil P King","David Veesler","Jesse D Bloom"],"journal":"Cell","doi":"10.1016/j.cell.2020.08.012","link":"https://www.sciencedirect.com/science/article/pii/S0092867420310035?via%3Dihub","image":"/assets/papers/2020_starr_a.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2020_starr_a.md","filePath":"papers/2020_starr_a.md"}'),r={name:"papers/2020_starr_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein mediates viral attachment to ACE2 receptor and is a major determinant of host range and a dominant target of neutralizing antibodies. Here, we experimentally measure how all amino acid mutations to the RBD affect expression of folded protein and its affinity for ACE2. Most mutations are deleterious for RBD expression and ACE2 binding, and we identify constrained regions on the RBD’s surface that may be desirable targets for vaccines and antibody-based therapeutics. But a substantial number of mutations are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses. However, we find no evidence that these ACE2-affinity-enhancing mutations have been selected in current SARS-CoV-2 pandemic isolates. We present an interactive visualization and open analysis pipeline to facilitate use of our dataset for vaccine design and functional annotation of mutations observed during viral surveillance.",-1),d=[o,s];function l(c,p,f,m,u,h){return t(),n("div",null,d)}const b=a(r,[["render",l]]);export{g as __pageData,b as default}; diff --git a/assets/papers_2020_xue.md.BsHUZbHn.js b/assets/papers_2020_xue.md.tetMVX9z.js similarity index 96% rename from assets/papers_2020_xue.md.BsHUZbHn.js rename to assets/papers_2020_xue.md.tetMVX9z.js index 2391a07..bc02410 100644 --- a/assets/papers_2020_xue.md.BsHUZbHn.js +++ b/assets/papers_2020_xue.md.tetMVX9z.js @@ -1 +1 @@ -import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Linking influenza virus evolution within and between human hosts","description":"","frontmatter":{"layout":"paper","title":"Linking influenza virus evolution within and between human hosts","date":"2020-01-01","authors":["Katherine S Xue","Jesse D Bloom"],"journal":"Virus evolution","doi":"10.1093/ve/veaa010","link":"https://academic.oup.com/ve/article/6/1/veaa010/5739536","image":"/assets/papers/2020_xue.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2020_xue.md","filePath":"papers/2020_xue.md"}'),s={name:"papers/2020_xue.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza viruses rapidly diversify within individual human infections. Several recent studies have deep-sequenced clinical influenza infections to identify viral variation within hosts, but it remains unclear how within-host mutations fare at the between-host scale. Here, we compare the genetic variation of H3N2 influenza within and between hosts to link viral evolutionary dynamics across scales. Synonymous sites evolve at similar rates at both scales, indicating that global evolution at these putatively neutral sites results from the accumulation of within-host variation. However, nonsynonymous mutations are depleted between hosts compared to within hosts, suggesting that selection purges many of the protein-altering changes that arise within hosts. The exception is at antigenic sites, where selection detectably favors nonsynonymous mutations at the global scale, but not within hosts. These results suggest that selection against deleterious mutations and selection for antigenic change are the main forces that act on within-host variants of influenza virus as they transmit and circulate between hosts.",-1),l=[o,r];function h(c,u,d,m,p,v){return n(),a("div",null,l)}const w=t(s,[["render",h]]);export{_ as __pageData,w as default}; +import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Linking influenza virus evolution within and between human hosts","description":"","frontmatter":{"layout":"paper","title":"Linking influenza virus evolution within and between human hosts","date":"2020-01-01","authors":["Katherine S Xue","Jesse D Bloom"],"journal":"Virus evolution","doi":"10.1093/ve/veaa010","link":"https://academic.oup.com/ve/article/6/1/veaa010/5739536","image":"/assets/papers/2020_xue.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2020_xue.md","filePath":"papers/2020_xue.md"}'),s={name:"papers/2020_xue.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza viruses rapidly diversify within individual human infections. Several recent studies have deep-sequenced clinical influenza infections to identify viral variation within hosts, but it remains unclear how within-host mutations fare at the between-host scale. Here, we compare the genetic variation of H3N2 influenza within and between hosts to link viral evolutionary dynamics across scales. Synonymous sites evolve at similar rates at both scales, indicating that global evolution at these putatively neutral sites results from the accumulation of within-host variation. However, nonsynonymous mutations are depleted between hosts compared to within hosts, suggesting that selection purges many of the protein-altering changes that arise within hosts. The exception is at antigenic sites, where selection detectably favors nonsynonymous mutations at the global scale, but not within hosts. These results suggest that selection against deleterious mutations and selection for antigenic change are the main forces that act on within-host variants of influenza virus as they transmit and circulate between hosts.",-1),l=[o,r];function h(c,u,d,m,p,v){return n(),a("div",null,l)}const w=t(s,[["render",h]]);export{_ as __pageData,w as default}; diff --git a/assets/papers_2020_xue.md.BsHUZbHn.lean.js b/assets/papers_2020_xue.md.tetMVX9z.lean.js similarity index 96% rename from assets/papers_2020_xue.md.BsHUZbHn.lean.js rename to assets/papers_2020_xue.md.tetMVX9z.lean.js index 2391a07..bc02410 100644 --- a/assets/papers_2020_xue.md.BsHUZbHn.lean.js +++ b/assets/papers_2020_xue.md.tetMVX9z.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Linking influenza virus evolution within and between human hosts","description":"","frontmatter":{"layout":"paper","title":"Linking influenza virus evolution within and between human hosts","date":"2020-01-01","authors":["Katherine S Xue","Jesse D Bloom"],"journal":"Virus evolution","doi":"10.1093/ve/veaa010","link":"https://academic.oup.com/ve/article/6/1/veaa010/5739536","image":"/assets/papers/2020_xue.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2020_xue.md","filePath":"papers/2020_xue.md"}'),s={name:"papers/2020_xue.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza viruses rapidly diversify within individual human infections. Several recent studies have deep-sequenced clinical influenza infections to identify viral variation within hosts, but it remains unclear how within-host mutations fare at the between-host scale. Here, we compare the genetic variation of H3N2 influenza within and between hosts to link viral evolutionary dynamics across scales. Synonymous sites evolve at similar rates at both scales, indicating that global evolution at these putatively neutral sites results from the accumulation of within-host variation. However, nonsynonymous mutations are depleted between hosts compared to within hosts, suggesting that selection purges many of the protein-altering changes that arise within hosts. The exception is at antigenic sites, where selection detectably favors nonsynonymous mutations at the global scale, but not within hosts. These results suggest that selection against deleterious mutations and selection for antigenic change are the main forces that act on within-host variants of influenza virus as they transmit and circulate between hosts.",-1),l=[o,r];function h(c,u,d,m,p,v){return n(),a("div",null,l)}const w=t(s,[["render",h]]);export{_ as __pageData,w as default}; +import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Linking influenza virus evolution within and between human hosts","description":"","frontmatter":{"layout":"paper","title":"Linking influenza virus evolution within and between human hosts","date":"2020-01-01","authors":["Katherine S Xue","Jesse D Bloom"],"journal":"Virus evolution","doi":"10.1093/ve/veaa010","link":"https://academic.oup.com/ve/article/6/1/veaa010/5739536","image":"/assets/papers/2020_xue.jpg","keywords":["Influenza","Within-host evolution"]},"headers":[],"relativePath":"papers/2020_xue.md","filePath":"papers/2020_xue.md"}'),s={name:"papers/2020_xue.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza viruses rapidly diversify within individual human infections. Several recent studies have deep-sequenced clinical influenza infections to identify viral variation within hosts, but it remains unclear how within-host mutations fare at the between-host scale. Here, we compare the genetic variation of H3N2 influenza within and between hosts to link viral evolutionary dynamics across scales. Synonymous sites evolve at similar rates at both scales, indicating that global evolution at these putatively neutral sites results from the accumulation of within-host variation. However, nonsynonymous mutations are depleted between hosts compared to within hosts, suggesting that selection purges many of the protein-altering changes that arise within hosts. The exception is at antigenic sites, where selection detectably favors nonsynonymous mutations at the global scale, but not within hosts. These results suggest that selection against deleterious mutations and selection for antigenic change are the main forces that act on within-host variants of influenza virus as they transmit and circulate between hosts.",-1),l=[o,r];function h(c,u,d,m,p,v){return n(),a("div",null,l)}const w=t(s,[["render",h]]);export{_ as __pageData,w as default}; diff --git a/assets/papers_2021_bloom_a.md.B4IRJG9p.js b/assets/papers_2021_bloom_a.md.B20P_Vtx.js similarity index 92% rename from assets/papers_2021_bloom_a.md.B4IRJG9p.js rename to assets/papers_2021_bloom_a.md.B20P_Vtx.js index 69790fd..00c7122 100644 --- a/assets/papers_2021_bloom_a.md.B4IRJG9p.js +++ b/assets/papers_2021_bloom_a.md.B20P_Vtx.js @@ -1 +1 @@ -import{_ as t,c as a,o,b as e,d as s}from"./chunks/framework.BqSDeblO.js";const y=JSON.parse('{"title":"Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic","description":"","frontmatter":{"layout":"paper","title":"Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic","date":"2021-12-01","authors":["Jesse D Bloom"],"journal":"mBio","doi":"10.1093/molbev/msab246","link":"https://academic.oup.com/mbe/article/38/12/5211/6353034","image":"/assets/papers/2021_bloom_a.jpg","keywords":["SARS-CoV-2"]},"headers":[],"relativePath":"papers/2021_bloom_a.md","filePath":"papers/2021_bloom_a.md"}'),r={name:"papers/2021_bloom_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"The origin and early spread of SARS-CoV-2 remains shrouded in mystery. Here, I identify a data set containing SARS-CoV-2 sequences from early in the Wuhan epidemic that has been deleted from the NIH’s Sequence Read Archive. I recover the deleted files from the Google Cloud and reconstruct partial sequences of 13 early epidemic viruses. Phylogenetic analysis of these sequences in the context of carefully annotated existing data further supports the idea that the Huanan Seafood Market sequences are not fully representative of the viruses in Wuhan early in the epidemic. Instead, the progenitor of currently known SARS-CoV-2 sequences likely contained three mutations relative to the market viruses that made it more similar to SARS-CoV-2’s bat coronavirus relatives.",-1),d=[n,i];function c(l,h,m,p,u,_){return o(),a("div",null,d)}const b=t(r,[["render",c]]);export{y as __pageData,b as default}; +import{_ as t,c as a,o,b as e,d as s}from"./chunks/framework.D4bY2S_W.js";const y=JSON.parse('{"title":"Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic","description":"","frontmatter":{"layout":"paper","title":"Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic","date":"2021-12-01","authors":["Jesse D Bloom"],"journal":"mBio","doi":"10.1093/molbev/msab246","link":"https://academic.oup.com/mbe/article/38/12/5211/6353034","image":"/assets/papers/2021_bloom_a.jpg","keywords":["SARS-CoV-2"]},"headers":[],"relativePath":"papers/2021_bloom_a.md","filePath":"papers/2021_bloom_a.md"}'),r={name:"papers/2021_bloom_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"The origin and early spread of SARS-CoV-2 remains shrouded in mystery. Here, I identify a data set containing SARS-CoV-2 sequences from early in the Wuhan epidemic that has been deleted from the NIH’s Sequence Read Archive. I recover the deleted files from the Google Cloud and reconstruct partial sequences of 13 early epidemic viruses. Phylogenetic analysis of these sequences in the context of carefully annotated existing data further supports the idea that the Huanan Seafood Market sequences are not fully representative of the viruses in Wuhan early in the epidemic. Instead, the progenitor of currently known SARS-CoV-2 sequences likely contained three mutations relative to the market viruses that made it more similar to SARS-CoV-2’s bat coronavirus relatives.",-1),d=[n,i];function c(l,h,m,p,u,_){return o(),a("div",null,d)}const b=t(r,[["render",c]]);export{y as __pageData,b as default}; diff --git a/assets/papers_2021_bloom_a.md.B4IRJG9p.lean.js b/assets/papers_2021_bloom_a.md.B20P_Vtx.lean.js similarity index 92% rename from assets/papers_2021_bloom_a.md.B4IRJG9p.lean.js rename to assets/papers_2021_bloom_a.md.B20P_Vtx.lean.js index 69790fd..00c7122 100644 --- a/assets/papers_2021_bloom_a.md.B4IRJG9p.lean.js +++ b/assets/papers_2021_bloom_a.md.B20P_Vtx.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o,b as e,d as s}from"./chunks/framework.BqSDeblO.js";const y=JSON.parse('{"title":"Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic","description":"","frontmatter":{"layout":"paper","title":"Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic","date":"2021-12-01","authors":["Jesse D Bloom"],"journal":"mBio","doi":"10.1093/molbev/msab246","link":"https://academic.oup.com/mbe/article/38/12/5211/6353034","image":"/assets/papers/2021_bloom_a.jpg","keywords":["SARS-CoV-2"]},"headers":[],"relativePath":"papers/2021_bloom_a.md","filePath":"papers/2021_bloom_a.md"}'),r={name:"papers/2021_bloom_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"The origin and early spread of SARS-CoV-2 remains shrouded in mystery. Here, I identify a data set containing SARS-CoV-2 sequences from early in the Wuhan epidemic that has been deleted from the NIH’s Sequence Read Archive. I recover the deleted files from the Google Cloud and reconstruct partial sequences of 13 early epidemic viruses. Phylogenetic analysis of these sequences in the context of carefully annotated existing data further supports the idea that the Huanan Seafood Market sequences are not fully representative of the viruses in Wuhan early in the epidemic. Instead, the progenitor of currently known SARS-CoV-2 sequences likely contained three mutations relative to the market viruses that made it more similar to SARS-CoV-2’s bat coronavirus relatives.",-1),d=[n,i];function c(l,h,m,p,u,_){return o(),a("div",null,d)}const b=t(r,[["render",c]]);export{y as __pageData,b as default}; +import{_ as t,c as a,o,b as e,d as s}from"./chunks/framework.D4bY2S_W.js";const y=JSON.parse('{"title":"Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic","description":"","frontmatter":{"layout":"paper","title":"Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic","date":"2021-12-01","authors":["Jesse D Bloom"],"journal":"mBio","doi":"10.1093/molbev/msab246","link":"https://academic.oup.com/mbe/article/38/12/5211/6353034","image":"/assets/papers/2021_bloom_a.jpg","keywords":["SARS-CoV-2"]},"headers":[],"relativePath":"papers/2021_bloom_a.md","filePath":"papers/2021_bloom_a.md"}'),r={name:"papers/2021_bloom_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"The origin and early spread of SARS-CoV-2 remains shrouded in mystery. Here, I identify a data set containing SARS-CoV-2 sequences from early in the Wuhan epidemic that has been deleted from the NIH’s Sequence Read Archive. I recover the deleted files from the Google Cloud and reconstruct partial sequences of 13 early epidemic viruses. Phylogenetic analysis of these sequences in the context of carefully annotated existing data further supports the idea that the Huanan Seafood Market sequences are not fully representative of the viruses in Wuhan early in the epidemic. Instead, the progenitor of currently known SARS-CoV-2 sequences likely contained three mutations relative to the market viruses that made it more similar to SARS-CoV-2’s bat coronavirus relatives.",-1),d=[n,i];function c(l,h,m,p,u,_){return o(),a("div",null,d)}const b=t(r,[["render",c]]);export{y as __pageData,b as default}; diff --git a/assets/papers_2021_crawford.md.B2O4W4th.js b/assets/papers_2021_crawford.md.LqRx9oAP.js similarity index 97% rename from assets/papers_2021_crawford.md.B2O4W4th.js rename to assets/papers_2021_crawford.md.LqRx9oAP.js index f945055..e85ea7e 100644 --- a/assets/papers_2021_crawford.md.B2O4W4th.js +++ b/assets/papers_2021_crawford.md.LqRx9oAP.js @@ -1 +1 @@ -import{_ as t,c as a,o as i,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Dynamics of neutralizing antibody titers in the months after severe acute respiratory syndrome coronavirus 2 infection","description":"","frontmatter":{"layout":"paper","title":"Dynamics of neutralizing antibody titers in the months after severe acute respiratory syndrome coronavirus 2 infection","date":"2021-01-15","authors":["Katharine HD Crawford","Adam S Dingens","Rachel Eguia","Caitlin R Wolf","Naomi Wilcox","Jennifer K Logue","Kiel Shuey","Amanda M Casto","Brooke Fiala","Samuel Wrenn","Deleah Pettie","Neil P King","Alexander L Greninger","Helen Y Chu","Jesse D Bloom"],"journal":"The Journal of infectious diseases","doi":"10.1093/infdis/jiaa618","link":"https://academic.oup.com/jid/article/223/2/197/5916372","image":"/assets/papers/2021_crawford.jpg","keywords":["SARS-CoV-2","Immunity","Pseudovirus"]},"headers":[],"relativePath":"papers/2021_crawford.md","filePath":"papers/2021_crawford.md"}'),r={name:"papers/2021_crawford.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop neutralizing antibodies that target the viral spike protein. In this study, we quantified how levels of these antibodies change in the months after SARS-CoV-2 infection by examining longitudinal samples collected approximately 30–152 days after symptom onset from a prospective cohort of 32 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about 4-fold from 1 to 4 months after symptom onset. This decline in neutralizing antibody titers was accompanied by a decline in total antibodies capable of binding the viral spike protein or its receptor-binding domain. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.",-1),d=[n,s];function l(c,m,p,f,u,h){return i(),a("div",null,d)}const v=t(r,[["render",l]]);export{b as __pageData,v as default}; +import{_ as t,c as a,o as i,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Dynamics of neutralizing antibody titers in the months after severe acute respiratory syndrome coronavirus 2 infection","description":"","frontmatter":{"layout":"paper","title":"Dynamics of neutralizing antibody titers in the months after severe acute respiratory syndrome coronavirus 2 infection","date":"2021-01-15","authors":["Katharine HD Crawford","Adam S Dingens","Rachel Eguia","Caitlin R Wolf","Naomi Wilcox","Jennifer K Logue","Kiel Shuey","Amanda M Casto","Brooke Fiala","Samuel Wrenn","Deleah Pettie","Neil P King","Alexander L Greninger","Helen Y Chu","Jesse D Bloom"],"journal":"The Journal of infectious diseases","doi":"10.1093/infdis/jiaa618","link":"https://academic.oup.com/jid/article/223/2/197/5916372","image":"/assets/papers/2021_crawford.jpg","keywords":["SARS-CoV-2","Immunity","Pseudovirus"]},"headers":[],"relativePath":"papers/2021_crawford.md","filePath":"papers/2021_crawford.md"}'),r={name:"papers/2021_crawford.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop neutralizing antibodies that target the viral spike protein. In this study, we quantified how levels of these antibodies change in the months after SARS-CoV-2 infection by examining longitudinal samples collected approximately 30–152 days after symptom onset from a prospective cohort of 32 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about 4-fold from 1 to 4 months after symptom onset. This decline in neutralizing antibody titers was accompanied by a decline in total antibodies capable of binding the viral spike protein or its receptor-binding domain. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.",-1),d=[n,s];function l(c,m,p,f,u,h){return i(),a("div",null,d)}const v=t(r,[["render",l]]);export{b as __pageData,v as default}; diff --git a/assets/papers_2021_crawford.md.B2O4W4th.lean.js b/assets/papers_2021_crawford.md.LqRx9oAP.lean.js similarity index 97% rename from assets/papers_2021_crawford.md.B2O4W4th.lean.js rename to assets/papers_2021_crawford.md.LqRx9oAP.lean.js index f945055..e85ea7e 100644 --- a/assets/papers_2021_crawford.md.B2O4W4th.lean.js +++ b/assets/papers_2021_crawford.md.LqRx9oAP.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as i,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Dynamics of neutralizing antibody titers in the months after severe acute respiratory syndrome coronavirus 2 infection","description":"","frontmatter":{"layout":"paper","title":"Dynamics of neutralizing antibody titers in the months after severe acute respiratory syndrome coronavirus 2 infection","date":"2021-01-15","authors":["Katharine HD Crawford","Adam S Dingens","Rachel Eguia","Caitlin R Wolf","Naomi Wilcox","Jennifer K Logue","Kiel Shuey","Amanda M Casto","Brooke Fiala","Samuel Wrenn","Deleah Pettie","Neil P King","Alexander L Greninger","Helen Y Chu","Jesse D Bloom"],"journal":"The Journal of infectious diseases","doi":"10.1093/infdis/jiaa618","link":"https://academic.oup.com/jid/article/223/2/197/5916372","image":"/assets/papers/2021_crawford.jpg","keywords":["SARS-CoV-2","Immunity","Pseudovirus"]},"headers":[],"relativePath":"papers/2021_crawford.md","filePath":"papers/2021_crawford.md"}'),r={name:"papers/2021_crawford.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop neutralizing antibodies that target the viral spike protein. In this study, we quantified how levels of these antibodies change in the months after SARS-CoV-2 infection by examining longitudinal samples collected approximately 30–152 days after symptom onset from a prospective cohort of 32 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about 4-fold from 1 to 4 months after symptom onset. This decline in neutralizing antibody titers was accompanied by a decline in total antibodies capable of binding the viral spike protein or its receptor-binding domain. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.",-1),d=[n,s];function l(c,m,p,f,u,h){return i(),a("div",null,d)}const v=t(r,[["render",l]]);export{b as __pageData,v as default}; +import{_ as t,c as a,o as i,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Dynamics of neutralizing antibody titers in the months after severe acute respiratory syndrome coronavirus 2 infection","description":"","frontmatter":{"layout":"paper","title":"Dynamics of neutralizing antibody titers in the months after severe acute respiratory syndrome coronavirus 2 infection","date":"2021-01-15","authors":["Katharine HD Crawford","Adam S Dingens","Rachel Eguia","Caitlin R Wolf","Naomi Wilcox","Jennifer K Logue","Kiel Shuey","Amanda M Casto","Brooke Fiala","Samuel Wrenn","Deleah Pettie","Neil P King","Alexander L Greninger","Helen Y Chu","Jesse D Bloom"],"journal":"The Journal of infectious diseases","doi":"10.1093/infdis/jiaa618","link":"https://academic.oup.com/jid/article/223/2/197/5916372","image":"/assets/papers/2021_crawford.jpg","keywords":["SARS-CoV-2","Immunity","Pseudovirus"]},"headers":[],"relativePath":"papers/2021_crawford.md","filePath":"papers/2021_crawford.md"}'),r={name:"papers/2021_crawford.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop neutralizing antibodies that target the viral spike protein. In this study, we quantified how levels of these antibodies change in the months after SARS-CoV-2 infection by examining longitudinal samples collected approximately 30–152 days after symptom onset from a prospective cohort of 32 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about 4-fold from 1 to 4 months after symptom onset. This decline in neutralizing antibody titers was accompanied by a decline in total antibodies capable of binding the viral spike protein or its receptor-binding domain. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.",-1),d=[n,s];function l(c,m,p,f,u,h){return i(),a("div",null,d)}const v=t(r,[["render",l]]);export{b as __pageData,v as default}; diff --git a/assets/papers_2021_dingens.md.yWYhT_0B.js b/assets/papers_2021_dingens.md.BpRmlWAS.js similarity index 97% rename from assets/papers_2021_dingens.md.yWYhT_0B.js rename to assets/papers_2021_dingens.md.BpRmlWAS.js index 4c941b7..9c29208 100644 --- a/assets/papers_2021_dingens.md.yWYhT_0B.js +++ b/assets/papers_2021_dingens.md.BpRmlWAS.js @@ -1 +1 @@ -import{_ as i,c as n,o as a,b as e,d as t}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination","description":"","frontmatter":{"layout":"paper","title":"High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination","date":"2021-01-13","authors":["Adam S Dingens","Payal Pratap","Keara Malone","Sarah K Hilton","Thomas Ketas","Christopher A Cottrell","Julie Overbaugh","John P Moore","PJ Klasse","Andrew B Ward","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.64281","link":"https://elifesciences.org/articles/64281","image":"/assets/papers/2021_dingens.jpg","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2021_dingens.md","filePath":"papers/2021_dingens.md"}'),o={name:"papers/2021_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Mapping polyclonal serum responses is critical to rational vaccine design. However, most high-resolution mapping approaches involve isolating and characterizing individual antibodies, which incompletely defines the polyclonal response. Here we use two complementary approaches to directly map the specificities of the neutralizing and binding antibodies of polyclonal anti-HIV-1 sera from rabbits immunized with BG505 Env SOSIP trimers. We used mutational antigenic profiling to determine how all mutations in Env affected viral neutralization and electron microscopy polyclonal epitope mapping (EMPEM) to directly visualize serum Fabs bound to Env trimers. The dominant neutralizing specificities were generally only a subset of the more diverse binding specificities. Additional differences between binding and neutralization reflected antigenicity differences between virus and soluble Env trimer. Furthermore, we refined residue-level epitope specificity directly from sera, revealing subtle differences across sera. Together, mutational antigenic profiling and EMPEM yield a holistic view of the binding and neutralizing specificity of polyclonal sera.",-1),l=[s,r];function c(d,p,f,m,g,h){return a(),n("div",null,l)}const v=i(o,[["render",c]]);export{b as __pageData,v as default}; +import{_ as i,c as n,o as a,b as e,d as t}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination","description":"","frontmatter":{"layout":"paper","title":"High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination","date":"2021-01-13","authors":["Adam S Dingens","Payal Pratap","Keara Malone","Sarah K Hilton","Thomas Ketas","Christopher A Cottrell","Julie Overbaugh","John P Moore","PJ Klasse","Andrew B Ward","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.64281","link":"https://elifesciences.org/articles/64281","image":"/assets/papers/2021_dingens.jpg","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2021_dingens.md","filePath":"papers/2021_dingens.md"}'),o={name:"papers/2021_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Mapping polyclonal serum responses is critical to rational vaccine design. However, most high-resolution mapping approaches involve isolating and characterizing individual antibodies, which incompletely defines the polyclonal response. Here we use two complementary approaches to directly map the specificities of the neutralizing and binding antibodies of polyclonal anti-HIV-1 sera from rabbits immunized with BG505 Env SOSIP trimers. We used mutational antigenic profiling to determine how all mutations in Env affected viral neutralization and electron microscopy polyclonal epitope mapping (EMPEM) to directly visualize serum Fabs bound to Env trimers. The dominant neutralizing specificities were generally only a subset of the more diverse binding specificities. Additional differences between binding and neutralization reflected antigenicity differences between virus and soluble Env trimer. Furthermore, we refined residue-level epitope specificity directly from sera, revealing subtle differences across sera. Together, mutational antigenic profiling and EMPEM yield a holistic view of the binding and neutralizing specificity of polyclonal sera.",-1),l=[s,r];function c(d,p,f,m,g,h){return a(),n("div",null,l)}const v=i(o,[["render",c]]);export{b as __pageData,v as default}; diff --git a/assets/papers_2021_dingens.md.yWYhT_0B.lean.js b/assets/papers_2021_dingens.md.BpRmlWAS.lean.js similarity index 97% rename from assets/papers_2021_dingens.md.yWYhT_0B.lean.js rename to assets/papers_2021_dingens.md.BpRmlWAS.lean.js index 4c941b7..9c29208 100644 --- a/assets/papers_2021_dingens.md.yWYhT_0B.lean.js +++ b/assets/papers_2021_dingens.md.BpRmlWAS.lean.js @@ -1 +1 @@ -import{_ as i,c as n,o as a,b as e,d as t}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination","description":"","frontmatter":{"layout":"paper","title":"High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination","date":"2021-01-13","authors":["Adam S Dingens","Payal Pratap","Keara Malone","Sarah K Hilton","Thomas Ketas","Christopher A Cottrell","Julie Overbaugh","John P Moore","PJ Klasse","Andrew B Ward","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.64281","link":"https://elifesciences.org/articles/64281","image":"/assets/papers/2021_dingens.jpg","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2021_dingens.md","filePath":"papers/2021_dingens.md"}'),o={name:"papers/2021_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Mapping polyclonal serum responses is critical to rational vaccine design. However, most high-resolution mapping approaches involve isolating and characterizing individual antibodies, which incompletely defines the polyclonal response. Here we use two complementary approaches to directly map the specificities of the neutralizing and binding antibodies of polyclonal anti-HIV-1 sera from rabbits immunized with BG505 Env SOSIP trimers. We used mutational antigenic profiling to determine how all mutations in Env affected viral neutralization and electron microscopy polyclonal epitope mapping (EMPEM) to directly visualize serum Fabs bound to Env trimers. The dominant neutralizing specificities were generally only a subset of the more diverse binding specificities. Additional differences between binding and neutralization reflected antigenicity differences between virus and soluble Env trimer. Furthermore, we refined residue-level epitope specificity directly from sera, revealing subtle differences across sera. Together, mutational antigenic profiling and EMPEM yield a holistic view of the binding and neutralizing specificity of polyclonal sera.",-1),l=[s,r];function c(d,p,f,m,g,h){return a(),n("div",null,l)}const v=i(o,[["render",c]]);export{b as __pageData,v as default}; +import{_ as i,c as n,o as a,b as e,d as t}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination","description":"","frontmatter":{"layout":"paper","title":"High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination","date":"2021-01-13","authors":["Adam S Dingens","Payal Pratap","Keara Malone","Sarah K Hilton","Thomas Ketas","Christopher A Cottrell","Julie Overbaugh","John P Moore","PJ Klasse","Andrew B Ward","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.64281","link":"https://elifesciences.org/articles/64281","image":"/assets/papers/2021_dingens.jpg","keywords":["HIV","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2021_dingens.md","filePath":"papers/2021_dingens.md"}'),o={name:"papers/2021_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Mapping polyclonal serum responses is critical to rational vaccine design. However, most high-resolution mapping approaches involve isolating and characterizing individual antibodies, which incompletely defines the polyclonal response. Here we use two complementary approaches to directly map the specificities of the neutralizing and binding antibodies of polyclonal anti-HIV-1 sera from rabbits immunized with BG505 Env SOSIP trimers. We used mutational antigenic profiling to determine how all mutations in Env affected viral neutralization and electron microscopy polyclonal epitope mapping (EMPEM) to directly visualize serum Fabs bound to Env trimers. The dominant neutralizing specificities were generally only a subset of the more diverse binding specificities. Additional differences between binding and neutralization reflected antigenicity differences between virus and soluble Env trimer. Furthermore, we refined residue-level epitope specificity directly from sera, revealing subtle differences across sera. Together, mutational antigenic profiling and EMPEM yield a holistic view of the binding and neutralizing specificity of polyclonal sera.",-1),l=[s,r];function c(d,p,f,m,g,h){return a(),n("div",null,l)}const v=i(o,[["render",c]]);export{b as __pageData,v as default}; diff --git a/assets/papers_2021_eguia.md.CK58XKY9.js b/assets/papers_2021_eguia.md.BxoLaVWQ.js similarity index 97% rename from assets/papers_2021_eguia.md.CK58XKY9.js rename to assets/papers_2021_eguia.md.BxoLaVWQ.js index bf8c116..2f2ff4e 100644 --- a/assets/papers_2021_eguia.md.CK58XKY9.js +++ b/assets/papers_2021_eguia.md.BxoLaVWQ.js @@ -1 +1 @@ -import{_ as a,c as t,o as i,b as e,d as s}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"A human coronavirus evolves antigenically to escape antibody immunity","description":"","frontmatter":{"layout":"paper","title":"A human coronavirus evolves antigenically to escape antibody immunity","date":"2021-04-08","authors":["Rachel T Eguia","Katharine HD Crawford","Terry Stevens-Ayers","Laurel Kelnhofer-Millevolte","Alexander L Greninger","Janet A Englund","Michael J Boeckh","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1009453","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009453","image":"/assets/papers/2021_eguia.png","keywords":["Coronavirus","Immunity"]},"headers":[],"relativePath":"papers/2021_eguia.md","filePath":"papers/2021_eguia.md"}'),o={name:"papers/2021_eguia.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"There is intense interest in antibody immunity to coronaviruses. However, it is unknown if coronaviruses evolve to escape such immunity, and if so, how rapidly. Here we address this question by characterizing the historical evolution of human coronavirus 229E. We identify human sera from the 1980s and 1990s that have neutralizing titers against contemporaneous 229E that are comparable to the anti-SARS-CoV-2 titers induced by SARS-CoV-2 infection or vaccination. We test these sera against 229E strains isolated after sera collection, and find that neutralizing titers are lower against these “future” viruses. In some cases, sera that neutralize contemporaneous 229E viral strains with titers >1:100 do not detectably neutralize strains isolated 8–17 years later. The decreased neutralization of “future” viruses is due to antigenic evolution of the viral spike, especially in the receptor-binding domain. If these results extrapolate to other coronaviruses, then it may be advisable to periodically update SARS-CoV-2 vaccines.",-1),l=[r,n];function c(u,d,h,p,m,v){return i(),t("div",null,l)}const y=a(o,[["render",c]]);export{g as __pageData,y as default}; +import{_ as a,c as t,o as i,b as e,d as s}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"A human coronavirus evolves antigenically to escape antibody immunity","description":"","frontmatter":{"layout":"paper","title":"A human coronavirus evolves antigenically to escape antibody immunity","date":"2021-04-08","authors":["Rachel T Eguia","Katharine HD Crawford","Terry Stevens-Ayers","Laurel Kelnhofer-Millevolte","Alexander L Greninger","Janet A Englund","Michael J Boeckh","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1009453","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009453","image":"/assets/papers/2021_eguia.png","keywords":["Coronavirus","Immunity"]},"headers":[],"relativePath":"papers/2021_eguia.md","filePath":"papers/2021_eguia.md"}'),o={name:"papers/2021_eguia.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"There is intense interest in antibody immunity to coronaviruses. However, it is unknown if coronaviruses evolve to escape such immunity, and if so, how rapidly. Here we address this question by characterizing the historical evolution of human coronavirus 229E. We identify human sera from the 1980s and 1990s that have neutralizing titers against contemporaneous 229E that are comparable to the anti-SARS-CoV-2 titers induced by SARS-CoV-2 infection or vaccination. We test these sera against 229E strains isolated after sera collection, and find that neutralizing titers are lower against these “future” viruses. In some cases, sera that neutralize contemporaneous 229E viral strains with titers >1:100 do not detectably neutralize strains isolated 8–17 years later. The decreased neutralization of “future” viruses is due to antigenic evolution of the viral spike, especially in the receptor-binding domain. If these results extrapolate to other coronaviruses, then it may be advisable to periodically update SARS-CoV-2 vaccines.",-1),l=[r,n];function c(u,d,h,p,m,v){return i(),t("div",null,l)}const y=a(o,[["render",c]]);export{g as __pageData,y as default}; diff --git a/assets/papers_2021_eguia.md.CK58XKY9.lean.js b/assets/papers_2021_eguia.md.BxoLaVWQ.lean.js similarity index 97% rename from assets/papers_2021_eguia.md.CK58XKY9.lean.js rename to assets/papers_2021_eguia.md.BxoLaVWQ.lean.js index bf8c116..2f2ff4e 100644 --- a/assets/papers_2021_eguia.md.CK58XKY9.lean.js +++ b/assets/papers_2021_eguia.md.BxoLaVWQ.lean.js @@ -1 +1 @@ -import{_ as a,c as t,o as i,b as e,d as s}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"A human coronavirus evolves antigenically to escape antibody immunity","description":"","frontmatter":{"layout":"paper","title":"A human coronavirus evolves antigenically to escape antibody immunity","date":"2021-04-08","authors":["Rachel T Eguia","Katharine HD Crawford","Terry Stevens-Ayers","Laurel Kelnhofer-Millevolte","Alexander L Greninger","Janet A Englund","Michael J Boeckh","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1009453","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009453","image":"/assets/papers/2021_eguia.png","keywords":["Coronavirus","Immunity"]},"headers":[],"relativePath":"papers/2021_eguia.md","filePath":"papers/2021_eguia.md"}'),o={name:"papers/2021_eguia.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"There is intense interest in antibody immunity to coronaviruses. However, it is unknown if coronaviruses evolve to escape such immunity, and if so, how rapidly. Here we address this question by characterizing the historical evolution of human coronavirus 229E. We identify human sera from the 1980s and 1990s that have neutralizing titers against contemporaneous 229E that are comparable to the anti-SARS-CoV-2 titers induced by SARS-CoV-2 infection or vaccination. We test these sera against 229E strains isolated after sera collection, and find that neutralizing titers are lower against these “future” viruses. In some cases, sera that neutralize contemporaneous 229E viral strains with titers >1:100 do not detectably neutralize strains isolated 8–17 years later. The decreased neutralization of “future” viruses is due to antigenic evolution of the viral spike, especially in the receptor-binding domain. If these results extrapolate to other coronaviruses, then it may be advisable to periodically update SARS-CoV-2 vaccines.",-1),l=[r,n];function c(u,d,h,p,m,v){return i(),t("div",null,l)}const y=a(o,[["render",c]]);export{g as __pageData,y as default}; +import{_ as a,c as t,o as i,b as e,d as s}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"A human coronavirus evolves antigenically to escape antibody immunity","description":"","frontmatter":{"layout":"paper","title":"A human coronavirus evolves antigenically to escape antibody immunity","date":"2021-04-08","authors":["Rachel T Eguia","Katharine HD Crawford","Terry Stevens-Ayers","Laurel Kelnhofer-Millevolte","Alexander L Greninger","Janet A Englund","Michael J Boeckh","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1009453","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009453","image":"/assets/papers/2021_eguia.png","keywords":["Coronavirus","Immunity"]},"headers":[],"relativePath":"papers/2021_eguia.md","filePath":"papers/2021_eguia.md"}'),o={name:"papers/2021_eguia.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"There is intense interest in antibody immunity to coronaviruses. However, it is unknown if coronaviruses evolve to escape such immunity, and if so, how rapidly. Here we address this question by characterizing the historical evolution of human coronavirus 229E. We identify human sera from the 1980s and 1990s that have neutralizing titers against contemporaneous 229E that are comparable to the anti-SARS-CoV-2 titers induced by SARS-CoV-2 infection or vaccination. We test these sera against 229E strains isolated after sera collection, and find that neutralizing titers are lower against these “future” viruses. In some cases, sera that neutralize contemporaneous 229E viral strains with titers >1:100 do not detectably neutralize strains isolated 8–17 years later. The decreased neutralization of “future” viruses is due to antigenic evolution of the viral spike, especially in the receptor-binding domain. If these results extrapolate to other coronaviruses, then it may be advisable to periodically update SARS-CoV-2 vaccines.",-1),l=[r,n];function c(u,d,h,p,m,v){return i(),t("div",null,l)}const y=a(o,[["render",c]]);export{g as __pageData,y as default}; diff --git a/assets/papers_2021_greaney_a.md.DMqcDQdL.js b/assets/papers_2021_greaney_a.md.tqZcoDO4.js similarity index 97% rename from assets/papers_2021_greaney_a.md.DMqcDQdL.js rename to assets/papers_2021_greaney_a.md.tqZcoDO4.js index 55af221..126213a 100644 --- a/assets/papers_2021_greaney_a.md.DMqcDQdL.js +++ b/assets/papers_2021_greaney_a.md.tqZcoDO4.js @@ -1 +1 @@ -import{_ as a,c as t,o as s,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies","description":"","frontmatter":{"layout":"paper","title":"Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies","date":"2021-07-07","authors":["Allison J Greaney","Tyler N Starr","Christopher O Barnes","Yiska Weisblum","Fabian Schmidt","Marina Caskey","Christian Gaebler","Alice Cho","Marianna Agudelo","Shlomo Finkin","Zijun Wang","Daniel Poston","Frauke Muecksch","Theodora Hatziioannou","Paul D Bieniasz","Davide F Robbiani","Michel C Nussenzweig","Pamela J Bjorkman","Jesse D Bloom"],"journal":"Nature Communications","doi":"10.1038/s41467-021-24435-8","link":"https://www.nature.com/articles/s41467-021-24435-8","image":"/assets/papers/2021_greaney_a.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2021_greaney_a.md","filePath":"papers/2021_greaney_a.md"}'),o={name:"papers/2021_greaney_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasmas, including plasmas from individuals from whom some of the antibodies were isolated. While the binding of polyclonal plasma antibodies are affected by mutations across multiple RBD epitopes, the plasma-escape maps most resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is skewed towards a single class of antibodies targeting an epitope that is already undergoing rapid evolution.",-1),l=[n,r];function p(c,d,h,m,u,b){return s(),t("div",null,l)}const y=a(o,[["render",p]]);export{g as __pageData,y as default}; +import{_ as a,c as t,o as s,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies","description":"","frontmatter":{"layout":"paper","title":"Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies","date":"2021-07-07","authors":["Allison J Greaney","Tyler N Starr","Christopher O Barnes","Yiska Weisblum","Fabian Schmidt","Marina Caskey","Christian Gaebler","Alice Cho","Marianna Agudelo","Shlomo Finkin","Zijun Wang","Daniel Poston","Frauke Muecksch","Theodora Hatziioannou","Paul D Bieniasz","Davide F Robbiani","Michel C Nussenzweig","Pamela J Bjorkman","Jesse D Bloom"],"journal":"Nature Communications","doi":"10.1038/s41467-021-24435-8","link":"https://www.nature.com/articles/s41467-021-24435-8","image":"/assets/papers/2021_greaney_a.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2021_greaney_a.md","filePath":"papers/2021_greaney_a.md"}'),o={name:"papers/2021_greaney_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasmas, including plasmas from individuals from whom some of the antibodies were isolated. While the binding of polyclonal plasma antibodies are affected by mutations across multiple RBD epitopes, the plasma-escape maps most resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is skewed towards a single class of antibodies targeting an epitope that is already undergoing rapid evolution.",-1),l=[n,r];function p(c,d,h,m,u,b){return s(),t("div",null,l)}const y=a(o,[["render",p]]);export{g as __pageData,y as default}; diff --git a/assets/papers_2021_greaney_a.md.DMqcDQdL.lean.js b/assets/papers_2021_greaney_a.md.tqZcoDO4.lean.js similarity index 97% rename from assets/papers_2021_greaney_a.md.DMqcDQdL.lean.js rename to assets/papers_2021_greaney_a.md.tqZcoDO4.lean.js index 55af221..126213a 100644 --- a/assets/papers_2021_greaney_a.md.DMqcDQdL.lean.js +++ b/assets/papers_2021_greaney_a.md.tqZcoDO4.lean.js @@ -1 +1 @@ -import{_ as a,c as t,o as s,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies","description":"","frontmatter":{"layout":"paper","title":"Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies","date":"2021-07-07","authors":["Allison J Greaney","Tyler N Starr","Christopher O Barnes","Yiska Weisblum","Fabian Schmidt","Marina Caskey","Christian Gaebler","Alice Cho","Marianna Agudelo","Shlomo Finkin","Zijun Wang","Daniel Poston","Frauke Muecksch","Theodora Hatziioannou","Paul D Bieniasz","Davide F Robbiani","Michel C Nussenzweig","Pamela J Bjorkman","Jesse D Bloom"],"journal":"Nature Communications","doi":"10.1038/s41467-021-24435-8","link":"https://www.nature.com/articles/s41467-021-24435-8","image":"/assets/papers/2021_greaney_a.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2021_greaney_a.md","filePath":"papers/2021_greaney_a.md"}'),o={name:"papers/2021_greaney_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasmas, including plasmas from individuals from whom some of the antibodies were isolated. While the binding of polyclonal plasma antibodies are affected by mutations across multiple RBD epitopes, the plasma-escape maps most resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is skewed towards a single class of antibodies targeting an epitope that is already undergoing rapid evolution.",-1),l=[n,r];function p(c,d,h,m,u,b){return s(),t("div",null,l)}const y=a(o,[["render",p]]);export{g as __pageData,y as default}; +import{_ as a,c as t,o as s,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies","description":"","frontmatter":{"layout":"paper","title":"Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies","date":"2021-07-07","authors":["Allison J Greaney","Tyler N Starr","Christopher O Barnes","Yiska Weisblum","Fabian Schmidt","Marina Caskey","Christian Gaebler","Alice Cho","Marianna Agudelo","Shlomo Finkin","Zijun Wang","Daniel Poston","Frauke Muecksch","Theodora Hatziioannou","Paul D Bieniasz","Davide F Robbiani","Michel C Nussenzweig","Pamela J Bjorkman","Jesse D Bloom"],"journal":"Nature Communications","doi":"10.1038/s41467-021-24435-8","link":"https://www.nature.com/articles/s41467-021-24435-8","image":"/assets/papers/2021_greaney_a.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2021_greaney_a.md","filePath":"papers/2021_greaney_a.md"}'),o={name:"papers/2021_greaney_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasmas, including plasmas from individuals from whom some of the antibodies were isolated. While the binding of polyclonal plasma antibodies are affected by mutations across multiple RBD epitopes, the plasma-escape maps most resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is skewed towards a single class of antibodies targeting an epitope that is already undergoing rapid evolution.",-1),l=[n,r];function p(c,d,h,m,u,b){return s(),t("div",null,l)}const y=a(o,[["render",p]]);export{g as __pageData,y as default}; diff --git a/assets/papers_2021_greaney_b.md.CnbjCZwe.js b/assets/papers_2021_greaney_b.md.C70H2abN.js similarity index 97% rename from assets/papers_2021_greaney_b.md.CnbjCZwe.js rename to assets/papers_2021_greaney_b.md.C70H2abN.js index f78c23c..8aacb18 100644 --- a/assets/papers_2021_greaney_b.md.CnbjCZwe.js +++ b/assets/papers_2021_greaney_b.md.C70H2abN.js @@ -1 +1 @@ -import{_ as i,c as t,o as a,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const f=JSON.parse('{"title":"Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection","description":"","frontmatter":{"layout":"paper","title":"Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection","date":"2021-06-30","authors":["Allison J Greaney","Andrea N Loes","Lauren E Gentles","Katharine HD Crawford","Tyler N Starr","Keara D Malone","Helen Y Chu","Jesse D Bloom"],"journal":"Science translational medicine","doi":"10.1126/scitranslmed.abi9915","link":"https://www.science.org/doi/full/10.1126/scitranslmed.abi9915","image":"/assets/papers/2021_greaney_b.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2021_greaney_b.md","filePath":"papers/2021_greaney_b.md"}'),n={name:"papers/2021_greaney_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with mutations in key antibody epitopes has raised concerns that antigenic evolution could erode adaptive immunity elicited by prior infection or vaccination. The susceptibility of immunity to viral evolution is shaped in part by the breadth of epitopes targeted by antibodies elicited by vaccination or natural infection. To investigate how human antibody responses to vaccines are influenced by viral mutations, we used deep mutational scanning to compare the specificity of polyclonal antibodies elicited by either two doses of the mRNA-1273 COVID-19 vaccine or natural infection with SARS-CoV-2. The neutralizing activity of vaccine-elicited antibodies was more targeted to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein compared to antibodies elicited by natural infection. However, within the RBD, binding of vaccine-elicited antibodies was more broadly distributed across epitopes compared to infection-elicited antibodies. This greater binding breadth means that single RBD mutations have less impact on neutralization by vaccine sera compared to convalescent sera. Therefore, antibody immunity acquired by natural infection or different modes of vaccination may have a differing susceptibility to erosion by SARS-CoV-2 evolution.",-1),c=[r,s];function d(l,b,p,m,h,u){return a(),t("div",null,c)}const _=i(n,[["render",d]]);export{f as __pageData,_ as default}; +import{_ as i,c as t,o as a,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const f=JSON.parse('{"title":"Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection","description":"","frontmatter":{"layout":"paper","title":"Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection","date":"2021-06-30","authors":["Allison J Greaney","Andrea N Loes","Lauren E Gentles","Katharine HD Crawford","Tyler N Starr","Keara D Malone","Helen Y Chu","Jesse D Bloom"],"journal":"Science translational medicine","doi":"10.1126/scitranslmed.abi9915","link":"https://www.science.org/doi/full/10.1126/scitranslmed.abi9915","image":"/assets/papers/2021_greaney_b.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2021_greaney_b.md","filePath":"papers/2021_greaney_b.md"}'),n={name:"papers/2021_greaney_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with mutations in key antibody epitopes has raised concerns that antigenic evolution could erode adaptive immunity elicited by prior infection or vaccination. The susceptibility of immunity to viral evolution is shaped in part by the breadth of epitopes targeted by antibodies elicited by vaccination or natural infection. To investigate how human antibody responses to vaccines are influenced by viral mutations, we used deep mutational scanning to compare the specificity of polyclonal antibodies elicited by either two doses of the mRNA-1273 COVID-19 vaccine or natural infection with SARS-CoV-2. The neutralizing activity of vaccine-elicited antibodies was more targeted to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein compared to antibodies elicited by natural infection. However, within the RBD, binding of vaccine-elicited antibodies was more broadly distributed across epitopes compared to infection-elicited antibodies. This greater binding breadth means that single RBD mutations have less impact on neutralization by vaccine sera compared to convalescent sera. Therefore, antibody immunity acquired by natural infection or different modes of vaccination may have a differing susceptibility to erosion by SARS-CoV-2 evolution.",-1),c=[r,s];function d(l,b,p,m,h,u){return a(),t("div",null,c)}const _=i(n,[["render",d]]);export{f as __pageData,_ as default}; diff --git a/assets/papers_2021_greaney_b.md.CnbjCZwe.lean.js b/assets/papers_2021_greaney_b.md.C70H2abN.lean.js similarity index 97% rename from assets/papers_2021_greaney_b.md.CnbjCZwe.lean.js rename to assets/papers_2021_greaney_b.md.C70H2abN.lean.js index f78c23c..8aacb18 100644 --- a/assets/papers_2021_greaney_b.md.CnbjCZwe.lean.js +++ b/assets/papers_2021_greaney_b.md.C70H2abN.lean.js @@ -1 +1 @@ -import{_ as i,c as t,o as a,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const f=JSON.parse('{"title":"Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection","description":"","frontmatter":{"layout":"paper","title":"Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection","date":"2021-06-30","authors":["Allison J Greaney","Andrea N Loes","Lauren E Gentles","Katharine HD Crawford","Tyler N Starr","Keara D Malone","Helen Y Chu","Jesse D Bloom"],"journal":"Science translational medicine","doi":"10.1126/scitranslmed.abi9915","link":"https://www.science.org/doi/full/10.1126/scitranslmed.abi9915","image":"/assets/papers/2021_greaney_b.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2021_greaney_b.md","filePath":"papers/2021_greaney_b.md"}'),n={name:"papers/2021_greaney_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with mutations in key antibody epitopes has raised concerns that antigenic evolution could erode adaptive immunity elicited by prior infection or vaccination. The susceptibility of immunity to viral evolution is shaped in part by the breadth of epitopes targeted by antibodies elicited by vaccination or natural infection. To investigate how human antibody responses to vaccines are influenced by viral mutations, we used deep mutational scanning to compare the specificity of polyclonal antibodies elicited by either two doses of the mRNA-1273 COVID-19 vaccine or natural infection with SARS-CoV-2. The neutralizing activity of vaccine-elicited antibodies was more targeted to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein compared to antibodies elicited by natural infection. However, within the RBD, binding of vaccine-elicited antibodies was more broadly distributed across epitopes compared to infection-elicited antibodies. This greater binding breadth means that single RBD mutations have less impact on neutralization by vaccine sera compared to convalescent sera. Therefore, antibody immunity acquired by natural infection or different modes of vaccination may have a differing susceptibility to erosion by SARS-CoV-2 evolution.",-1),c=[r,s];function d(l,b,p,m,h,u){return a(),t("div",null,c)}const _=i(n,[["render",d]]);export{f as __pageData,_ as default}; +import{_ as i,c as t,o as a,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const f=JSON.parse('{"title":"Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection","description":"","frontmatter":{"layout":"paper","title":"Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection","date":"2021-06-30","authors":["Allison J Greaney","Andrea N Loes","Lauren E Gentles","Katharine HD Crawford","Tyler N Starr","Keara D Malone","Helen Y Chu","Jesse D Bloom"],"journal":"Science translational medicine","doi":"10.1126/scitranslmed.abi9915","link":"https://www.science.org/doi/full/10.1126/scitranslmed.abi9915","image":"/assets/papers/2021_greaney_b.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2021_greaney_b.md","filePath":"papers/2021_greaney_b.md"}'),n={name:"papers/2021_greaney_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with mutations in key antibody epitopes has raised concerns that antigenic evolution could erode adaptive immunity elicited by prior infection or vaccination. The susceptibility of immunity to viral evolution is shaped in part by the breadth of epitopes targeted by antibodies elicited by vaccination or natural infection. To investigate how human antibody responses to vaccines are influenced by viral mutations, we used deep mutational scanning to compare the specificity of polyclonal antibodies elicited by either two doses of the mRNA-1273 COVID-19 vaccine or natural infection with SARS-CoV-2. The neutralizing activity of vaccine-elicited antibodies was more targeted to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein compared to antibodies elicited by natural infection. However, within the RBD, binding of vaccine-elicited antibodies was more broadly distributed across epitopes compared to infection-elicited antibodies. This greater binding breadth means that single RBD mutations have less impact on neutralization by vaccine sera compared to convalescent sera. Therefore, antibody immunity acquired by natural infection or different modes of vaccination may have a differing susceptibility to erosion by SARS-CoV-2 evolution.",-1),c=[r,s];function d(l,b,p,m,h,u){return a(),t("div",null,c)}const _=i(n,[["render",d]]);export{f as __pageData,_ as default}; diff --git a/assets/papers_2021_greaney_c.md.DAIX3FxH.js b/assets/papers_2021_greaney_c.md.DOMukqxr.js similarity index 97% rename from assets/papers_2021_greaney_c.md.DAIX3FxH.js rename to assets/papers_2021_greaney_c.md.DOMukqxr.js index f766a7c..5e41d36 100644 --- a/assets/papers_2021_greaney_c.md.DAIX3FxH.js +++ b/assets/papers_2021_greaney_c.md.DOMukqxr.js @@ -1 +1 @@ -import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies","description":"","frontmatter":{"layout":"paper","title":"Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies","date":"2021-03-10","authors":["Allison J Greaney","Andrea N Loes","Katharine HD Crawford","Tyler N Starr","Keara D Malone","Helen Y Chu","Jesse D Bloom"],"journal":"Cell host & microbe","doi":"10.1016/j.chom.2021.02.003","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(21)00082-2.pdf","image":"/assets/papers/2021_greaney_c.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2021_greaney_c.md","filePath":"papers/2021_greaney_c.md"}'),o={name:"papers/2021_greaney_c.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The evolution of SARS-CoV-2 could impair recognition of the virus by human antibody-mediated immunity. To facilitate prospective surveillance for such evolution, we map how convalescent plasma antibodies are impacted by all mutations to the spike’s receptor-binding domain (RBD), the main target of plasma neutralizing activity. Binding by polyclonal plasma antibodies is affected by mutations in three main epitopes in the RBD, but longitudinal samples reveal that the impact of these mutations on antibody binding varies substantially both among individuals and within the same individual over time. Despite this inter- and intra-person heterogeneity, the mutations that most reduce antibody binding usually occur at just a few sites in the RBD’s receptor-binding motif. The most important site is E484, where neutralization by some plasma is reduced >10-fold by several mutations, including one in the emerging 20H/501Y.V2 and 20J/501Y.V3 SARS-CoV-2 lineages. Going forward, these plasma escape maps can inform surveillance of SARS-CoV-2 evolution.",-1),l=[s,r];function c(m,d,p,h,u,b){return i(),t("div",null,l)}const y=a(o,[["render",c]]);export{g as __pageData,y as default}; +import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies","description":"","frontmatter":{"layout":"paper","title":"Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies","date":"2021-03-10","authors":["Allison J Greaney","Andrea N Loes","Katharine HD Crawford","Tyler N Starr","Keara D Malone","Helen Y Chu","Jesse D Bloom"],"journal":"Cell host & microbe","doi":"10.1016/j.chom.2021.02.003","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(21)00082-2.pdf","image":"/assets/papers/2021_greaney_c.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2021_greaney_c.md","filePath":"papers/2021_greaney_c.md"}'),o={name:"papers/2021_greaney_c.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The evolution of SARS-CoV-2 could impair recognition of the virus by human antibody-mediated immunity. To facilitate prospective surveillance for such evolution, we map how convalescent plasma antibodies are impacted by all mutations to the spike’s receptor-binding domain (RBD), the main target of plasma neutralizing activity. Binding by polyclonal plasma antibodies is affected by mutations in three main epitopes in the RBD, but longitudinal samples reveal that the impact of these mutations on antibody binding varies substantially both among individuals and within the same individual over time. Despite this inter- and intra-person heterogeneity, the mutations that most reduce antibody binding usually occur at just a few sites in the RBD’s receptor-binding motif. The most important site is E484, where neutralization by some plasma is reduced >10-fold by several mutations, including one in the emerging 20H/501Y.V2 and 20J/501Y.V3 SARS-CoV-2 lineages. Going forward, these plasma escape maps can inform surveillance of SARS-CoV-2 evolution.",-1),l=[s,r];function c(m,d,p,h,u,b){return i(),t("div",null,l)}const y=a(o,[["render",c]]);export{g as __pageData,y as default}; diff --git a/assets/papers_2021_greaney_c.md.DAIX3FxH.lean.js b/assets/papers_2021_greaney_c.md.DOMukqxr.lean.js similarity index 97% rename from assets/papers_2021_greaney_c.md.DAIX3FxH.lean.js rename to assets/papers_2021_greaney_c.md.DOMukqxr.lean.js index f766a7c..5e41d36 100644 --- a/assets/papers_2021_greaney_c.md.DAIX3FxH.lean.js +++ b/assets/papers_2021_greaney_c.md.DOMukqxr.lean.js @@ -1 +1 @@ -import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies","description":"","frontmatter":{"layout":"paper","title":"Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies","date":"2021-03-10","authors":["Allison J Greaney","Andrea N Loes","Katharine HD Crawford","Tyler N Starr","Keara D Malone","Helen Y Chu","Jesse D Bloom"],"journal":"Cell host & microbe","doi":"10.1016/j.chom.2021.02.003","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(21)00082-2.pdf","image":"/assets/papers/2021_greaney_c.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2021_greaney_c.md","filePath":"papers/2021_greaney_c.md"}'),o={name:"papers/2021_greaney_c.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The evolution of SARS-CoV-2 could impair recognition of the virus by human antibody-mediated immunity. To facilitate prospective surveillance for such evolution, we map how convalescent plasma antibodies are impacted by all mutations to the spike’s receptor-binding domain (RBD), the main target of plasma neutralizing activity. Binding by polyclonal plasma antibodies is affected by mutations in three main epitopes in the RBD, but longitudinal samples reveal that the impact of these mutations on antibody binding varies substantially both among individuals and within the same individual over time. Despite this inter- and intra-person heterogeneity, the mutations that most reduce antibody binding usually occur at just a few sites in the RBD’s receptor-binding motif. The most important site is E484, where neutralization by some plasma is reduced >10-fold by several mutations, including one in the emerging 20H/501Y.V2 and 20J/501Y.V3 SARS-CoV-2 lineages. Going forward, these plasma escape maps can inform surveillance of SARS-CoV-2 evolution.",-1),l=[s,r];function c(m,d,p,h,u,b){return i(),t("div",null,l)}const y=a(o,[["render",c]]);export{g as __pageData,y as default}; +import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies","description":"","frontmatter":{"layout":"paper","title":"Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies","date":"2021-03-10","authors":["Allison J Greaney","Andrea N Loes","Katharine HD Crawford","Tyler N Starr","Keara D Malone","Helen Y Chu","Jesse D Bloom"],"journal":"Cell host & microbe","doi":"10.1016/j.chom.2021.02.003","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(21)00082-2.pdf","image":"/assets/papers/2021_greaney_c.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2021_greaney_c.md","filePath":"papers/2021_greaney_c.md"}'),o={name:"papers/2021_greaney_c.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The evolution of SARS-CoV-2 could impair recognition of the virus by human antibody-mediated immunity. To facilitate prospective surveillance for such evolution, we map how convalescent plasma antibodies are impacted by all mutations to the spike’s receptor-binding domain (RBD), the main target of plasma neutralizing activity. Binding by polyclonal plasma antibodies is affected by mutations in three main epitopes in the RBD, but longitudinal samples reveal that the impact of these mutations on antibody binding varies substantially both among individuals and within the same individual over time. Despite this inter- and intra-person heterogeneity, the mutations that most reduce antibody binding usually occur at just a few sites in the RBD’s receptor-binding motif. The most important site is E484, where neutralization by some plasma is reduced >10-fold by several mutations, including one in the emerging 20H/501Y.V2 and 20J/501Y.V3 SARS-CoV-2 lineages. Going forward, these plasma escape maps can inform surveillance of SARS-CoV-2 evolution.",-1),l=[s,r];function c(m,d,p,h,u,b){return i(),t("div",null,l)}const y=a(o,[["render",c]]);export{g as __pageData,y as default}; diff --git a/assets/papers_2021_greaney_d.md.Esuani1Z.js b/assets/papers_2021_greaney_d.md.B1gyjjsj.js similarity index 97% rename from assets/papers_2021_greaney_d.md.Esuani1Z.js rename to assets/papers_2021_greaney_d.md.B1gyjjsj.js index 46dcd3e..209072d 100644 --- a/assets/papers_2021_greaney_d.md.Esuani1Z.js +++ b/assets/papers_2021_greaney_d.md.B1gyjjsj.js @@ -1 +1 @@ -import{_ as a,c as t,o as n,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const f=JSON.parse('{"title":"Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition","description":"","frontmatter":{"layout":"paper","title":"Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition","date":"2021-01-13","authors":["Allison J Greaney*","Tyler N Starr*","Pavlo Gilchuk","Seth J Zost","Elad Binshtein","Andrea N Loes","Sarah K Hilton","John Huddleston","Rachel Eguia","Katharine HD Crawford","Adam S Dingens","Rachel S Nargi","Rachel E Sutton","Naveenchandra Suryadevara","Paul W Rothlauf","Zhuoming Liu","Sean PJ Whelan","Robert H Carnahan","James E Crowe","Jesse D Bloom"],"journal":"Cell host & microbe","doi":"10.1016/j.chom.2020.11.007","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(20)30624-7.pdf","image":"/assets/papers/2021_greaney_d.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2021_greaney_d.md","filePath":"papers/2021_greaney_d.md"}'),i={name:"papers/2021_greaney_d.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies. They further enable the design of escape-resistant antibody cocktails—including cocktails of antibodies that compete for binding to the same RBD surface but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution.",-1),c=[s,r];function d(l,p,h,m,u,g){return n(),t("div",null,c)}const _=a(i,[["render",d]]);export{f as __pageData,_ as default}; +import{_ as a,c as t,o as n,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const f=JSON.parse('{"title":"Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition","description":"","frontmatter":{"layout":"paper","title":"Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition","date":"2021-01-13","authors":["Allison J Greaney*","Tyler N Starr*","Pavlo Gilchuk","Seth J Zost","Elad Binshtein","Andrea N Loes","Sarah K Hilton","John Huddleston","Rachel Eguia","Katharine HD Crawford","Adam S Dingens","Rachel S Nargi","Rachel E Sutton","Naveenchandra Suryadevara","Paul W Rothlauf","Zhuoming Liu","Sean PJ Whelan","Robert H Carnahan","James E Crowe","Jesse D Bloom"],"journal":"Cell host & microbe","doi":"10.1016/j.chom.2020.11.007","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(20)30624-7.pdf","image":"/assets/papers/2021_greaney_d.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2021_greaney_d.md","filePath":"papers/2021_greaney_d.md"}'),i={name:"papers/2021_greaney_d.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies. They further enable the design of escape-resistant antibody cocktails—including cocktails of antibodies that compete for binding to the same RBD surface but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution.",-1),c=[s,r];function d(l,p,h,m,u,g){return n(),t("div",null,c)}const _=a(i,[["render",d]]);export{f as __pageData,_ as default}; diff --git a/assets/papers_2021_greaney_d.md.Esuani1Z.lean.js b/assets/papers_2021_greaney_d.md.B1gyjjsj.lean.js similarity index 97% rename from assets/papers_2021_greaney_d.md.Esuani1Z.lean.js rename to assets/papers_2021_greaney_d.md.B1gyjjsj.lean.js index 46dcd3e..209072d 100644 --- a/assets/papers_2021_greaney_d.md.Esuani1Z.lean.js +++ b/assets/papers_2021_greaney_d.md.B1gyjjsj.lean.js @@ -1 +1 @@ -import{_ as a,c as t,o as n,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const f=JSON.parse('{"title":"Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition","description":"","frontmatter":{"layout":"paper","title":"Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition","date":"2021-01-13","authors":["Allison J Greaney*","Tyler N Starr*","Pavlo Gilchuk","Seth J Zost","Elad Binshtein","Andrea N Loes","Sarah K Hilton","John Huddleston","Rachel Eguia","Katharine HD Crawford","Adam S Dingens","Rachel S Nargi","Rachel E Sutton","Naveenchandra Suryadevara","Paul W Rothlauf","Zhuoming Liu","Sean PJ Whelan","Robert H Carnahan","James E Crowe","Jesse D Bloom"],"journal":"Cell host & microbe","doi":"10.1016/j.chom.2020.11.007","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(20)30624-7.pdf","image":"/assets/papers/2021_greaney_d.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2021_greaney_d.md","filePath":"papers/2021_greaney_d.md"}'),i={name:"papers/2021_greaney_d.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies. They further enable the design of escape-resistant antibody cocktails—including cocktails of antibodies that compete for binding to the same RBD surface but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution.",-1),c=[s,r];function d(l,p,h,m,u,g){return n(),t("div",null,c)}const _=a(i,[["render",d]]);export{f as __pageData,_ as default}; +import{_ as a,c as t,o as n,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const f=JSON.parse('{"title":"Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition","description":"","frontmatter":{"layout":"paper","title":"Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition","date":"2021-01-13","authors":["Allison J Greaney*","Tyler N Starr*","Pavlo Gilchuk","Seth J Zost","Elad Binshtein","Andrea N Loes","Sarah K Hilton","John Huddleston","Rachel Eguia","Katharine HD Crawford","Adam S Dingens","Rachel S Nargi","Rachel E Sutton","Naveenchandra Suryadevara","Paul W Rothlauf","Zhuoming Liu","Sean PJ Whelan","Robert H Carnahan","James E Crowe","Jesse D Bloom"],"journal":"Cell host & microbe","doi":"10.1016/j.chom.2020.11.007","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(20)30624-7.pdf","image":"/assets/papers/2021_greaney_d.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2021_greaney_d.md","filePath":"papers/2021_greaney_d.md"}'),i={name:"papers/2021_greaney_d.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies. They further enable the design of escape-resistant antibody cocktails—including cocktails of antibodies that compete for binding to the same RBD surface but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution.",-1),c=[s,r];function d(l,p,h,m,u,g){return n(),t("div",null,c)}const _=a(i,[["render",d]]);export{f as __pageData,_ as default}; diff --git a/assets/papers_2021_greaney_welsh.md.lIZNODBW.js b/assets/papers_2021_greaney_welsh.md.DNVgkeUO.js similarity index 95% rename from assets/papers_2021_greaney_welsh.md.lIZNODBW.js rename to assets/papers_2021_greaney_welsh.md.DNVgkeUO.js index 19c4767..ddebf3f 100644 --- a/assets/papers_2021_greaney_welsh.md.lIZNODBW.js +++ b/assets/papers_2021_greaney_welsh.md.DNVgkeUO.js @@ -1 +1 @@ -import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution","description":"","frontmatter":{"layout":"paper","title":"Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution","date":"2021-04-20","authors":["Allison J Greaney","Frances C Welsh","Jesse D Bloom"],"journal":"Cell Reports Medicine","doi":"10.1016/j.xcrm.2021.100257","link":"https://www.sciencedirect.com/science/article/pii/S2666379121000732?via%3Dihub","image":"/assets/papers/2021_greaney_welsh.jpg","keywords":["Measles","Immunity"]},"headers":[],"relativePath":"papers/2021_greaney_welsh.md","filePath":"papers/2021_greaney_welsh.md"}'),n={name:"papers/2021_greaney_welsh.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Munoz-Alia and colleagues demonstrate that neutralizing antibody immunity to measles resists viral evolutionary escape because it targets numerous distinct viral epitopes. Their work contributes to our understanding of what determines whether a virus can evolve to evade immunity.",-1),l=[r,o];function c(d,m,p,u,_,h){return s(),a("div",null,l)}const v=t(n,[["render",c]]);export{g as __pageData,v as default}; +import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution","description":"","frontmatter":{"layout":"paper","title":"Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution","date":"2021-04-20","authors":["Allison J Greaney","Frances C Welsh","Jesse D Bloom"],"journal":"Cell Reports Medicine","doi":"10.1016/j.xcrm.2021.100257","link":"https://www.sciencedirect.com/science/article/pii/S2666379121000732?via%3Dihub","image":"/assets/papers/2021_greaney_welsh.jpg","keywords":["Measles","Immunity"]},"headers":[],"relativePath":"papers/2021_greaney_welsh.md","filePath":"papers/2021_greaney_welsh.md"}'),n={name:"papers/2021_greaney_welsh.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Munoz-Alia and colleagues demonstrate that neutralizing antibody immunity to measles resists viral evolutionary escape because it targets numerous distinct viral epitopes. Their work contributes to our understanding of what determines whether a virus can evolve to evade immunity.",-1),l=[r,o];function c(d,m,p,u,_,h){return s(),a("div",null,l)}const v=t(n,[["render",c]]);export{g as __pageData,v as default}; diff --git a/assets/papers_2021_greaney_welsh.md.lIZNODBW.lean.js b/assets/papers_2021_greaney_welsh.md.DNVgkeUO.lean.js similarity index 95% rename from assets/papers_2021_greaney_welsh.md.lIZNODBW.lean.js rename to assets/papers_2021_greaney_welsh.md.DNVgkeUO.lean.js index 19c4767..ddebf3f 100644 --- a/assets/papers_2021_greaney_welsh.md.lIZNODBW.lean.js +++ b/assets/papers_2021_greaney_welsh.md.DNVgkeUO.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution","description":"","frontmatter":{"layout":"paper","title":"Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution","date":"2021-04-20","authors":["Allison J Greaney","Frances C Welsh","Jesse D Bloom"],"journal":"Cell Reports Medicine","doi":"10.1016/j.xcrm.2021.100257","link":"https://www.sciencedirect.com/science/article/pii/S2666379121000732?via%3Dihub","image":"/assets/papers/2021_greaney_welsh.jpg","keywords":["Measles","Immunity"]},"headers":[],"relativePath":"papers/2021_greaney_welsh.md","filePath":"papers/2021_greaney_welsh.md"}'),n={name:"papers/2021_greaney_welsh.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Munoz-Alia and colleagues demonstrate that neutralizing antibody immunity to measles resists viral evolutionary escape because it targets numerous distinct viral epitopes. Their work contributes to our understanding of what determines whether a virus can evolve to evade immunity.",-1),l=[r,o];function c(d,m,p,u,_,h){return s(),a("div",null,l)}const v=t(n,[["render",c]]);export{g as __pageData,v as default}; +import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution","description":"","frontmatter":{"layout":"paper","title":"Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution","date":"2021-04-20","authors":["Allison J Greaney","Frances C Welsh","Jesse D Bloom"],"journal":"Cell Reports Medicine","doi":"10.1016/j.xcrm.2021.100257","link":"https://www.sciencedirect.com/science/article/pii/S2666379121000732?via%3Dihub","image":"/assets/papers/2021_greaney_welsh.jpg","keywords":["Measles","Immunity"]},"headers":[],"relativePath":"papers/2021_greaney_welsh.md","filePath":"papers/2021_greaney_welsh.md"}'),n={name:"papers/2021_greaney_welsh.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Munoz-Alia and colleagues demonstrate that neutralizing antibody immunity to measles resists viral evolutionary escape because it targets numerous distinct viral epitopes. Their work contributes to our understanding of what determines whether a virus can evolve to evade immunity.",-1),l=[r,o];function c(d,m,p,u,_,h){return s(),a("div",null,l)}const v=t(n,[["render",c]]);export{g as __pageData,v as default}; diff --git a/assets/papers_2021_soh.md.BF8RCYby.js b/assets/papers_2021_soh.md.BI0dWn0D.js similarity index 97% rename from assets/papers_2021_soh.md.BF8RCYby.js rename to assets/papers_2021_soh.md.BI0dWn0D.js index 9fb7bc6..f159147 100644 --- a/assets/papers_2021_soh.md.BF8RCYby.js +++ b/assets/papers_2021_soh.md.BI0dWn0D.js @@ -1 +1 @@ -import{_ as i,c as t,o as a,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Comprehensive profiling of mutations to influenza virus PB2 that confer resistance to the cap-binding inhibitor pimodivir","description":"","frontmatter":{"layout":"paper","title":"Comprehensive profiling of mutations to influenza virus PB2 that confer resistance to the cap-binding inhibitor pimodivir","date":"2021-06-22","authors":["Shirleen YQ Soh","Keara D Malone","Rachel T Eguia","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v13071196","link":"https://www.mdpi.com/1999-4915/13/7/1196","image":"/assets/papers/2021_soh.png","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2021_soh.md","filePath":"papers/2021_soh.md"}'),o={name:"papers/2021_soh.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Antivirals are used not only in the current treatment of influenza but are also stockpiled as a first line of defense against novel influenza strains for which vaccines have yet to be developed. Identifying drug resistance mutations can guide the clinical deployment of the antiviral and can additionally define the mechanisms of drug action and drug resistance. Pimodivir is a first-in-class inhibitor of the polymerase basic protein 2 (PB2) subunit of the influenza A virus polymerase complex. A number of resistance mutations have previously been identified in treated patients or cell culture. Here, we generate a complete map of the effect of all single-amino-acid mutations to an avian PB2 on resistance to pimodivir. We identified both known and novel resistance mutations not only in the previously implicated cap-binding and mid-link domains, but also in the N-terminal domain. Our complete map of pimodivir resistance thus enables the evaluation of whether new viral strains contain mutations that will confer pimodivir resistance.",-1),l=[s,r];function c(d,p,h,m,u,f){return a(),t("div",null,l)}const b=i(o,[["render",c]]);export{_ as __pageData,b as default}; +import{_ as i,c as t,o as a,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Comprehensive profiling of mutations to influenza virus PB2 that confer resistance to the cap-binding inhibitor pimodivir","description":"","frontmatter":{"layout":"paper","title":"Comprehensive profiling of mutations to influenza virus PB2 that confer resistance to the cap-binding inhibitor pimodivir","date":"2021-06-22","authors":["Shirleen YQ Soh","Keara D Malone","Rachel T Eguia","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v13071196","link":"https://www.mdpi.com/1999-4915/13/7/1196","image":"/assets/papers/2021_soh.png","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2021_soh.md","filePath":"papers/2021_soh.md"}'),o={name:"papers/2021_soh.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Antivirals are used not only in the current treatment of influenza but are also stockpiled as a first line of defense against novel influenza strains for which vaccines have yet to be developed. Identifying drug resistance mutations can guide the clinical deployment of the antiviral and can additionally define the mechanisms of drug action and drug resistance. Pimodivir is a first-in-class inhibitor of the polymerase basic protein 2 (PB2) subunit of the influenza A virus polymerase complex. A number of resistance mutations have previously been identified in treated patients or cell culture. Here, we generate a complete map of the effect of all single-amino-acid mutations to an avian PB2 on resistance to pimodivir. We identified both known and novel resistance mutations not only in the previously implicated cap-binding and mid-link domains, but also in the N-terminal domain. Our complete map of pimodivir resistance thus enables the evaluation of whether new viral strains contain mutations that will confer pimodivir resistance.",-1),l=[s,r];function c(d,p,h,m,u,f){return a(),t("div",null,l)}const b=i(o,[["render",c]]);export{_ as __pageData,b as default}; diff --git a/assets/papers_2021_soh.md.BF8RCYby.lean.js b/assets/papers_2021_soh.md.BI0dWn0D.lean.js similarity index 97% rename from assets/papers_2021_soh.md.BF8RCYby.lean.js rename to assets/papers_2021_soh.md.BI0dWn0D.lean.js index 9fb7bc6..f159147 100644 --- a/assets/papers_2021_soh.md.BF8RCYby.lean.js +++ b/assets/papers_2021_soh.md.BI0dWn0D.lean.js @@ -1 +1 @@ -import{_ as i,c as t,o as a,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Comprehensive profiling of mutations to influenza virus PB2 that confer resistance to the cap-binding inhibitor pimodivir","description":"","frontmatter":{"layout":"paper","title":"Comprehensive profiling of mutations to influenza virus PB2 that confer resistance to the cap-binding inhibitor pimodivir","date":"2021-06-22","authors":["Shirleen YQ Soh","Keara D Malone","Rachel T Eguia","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v13071196","link":"https://www.mdpi.com/1999-4915/13/7/1196","image":"/assets/papers/2021_soh.png","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2021_soh.md","filePath":"papers/2021_soh.md"}'),o={name:"papers/2021_soh.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Antivirals are used not only in the current treatment of influenza but are also stockpiled as a first line of defense against novel influenza strains for which vaccines have yet to be developed. Identifying drug resistance mutations can guide the clinical deployment of the antiviral and can additionally define the mechanisms of drug action and drug resistance. Pimodivir is a first-in-class inhibitor of the polymerase basic protein 2 (PB2) subunit of the influenza A virus polymerase complex. A number of resistance mutations have previously been identified in treated patients or cell culture. Here, we generate a complete map of the effect of all single-amino-acid mutations to an avian PB2 on resistance to pimodivir. We identified both known and novel resistance mutations not only in the previously implicated cap-binding and mid-link domains, but also in the N-terminal domain. Our complete map of pimodivir resistance thus enables the evaluation of whether new viral strains contain mutations that will confer pimodivir resistance.",-1),l=[s,r];function c(d,p,h,m,u,f){return a(),t("div",null,l)}const b=i(o,[["render",c]]);export{_ as __pageData,b as default}; +import{_ as i,c as t,o as a,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Comprehensive profiling of mutations to influenza virus PB2 that confer resistance to the cap-binding inhibitor pimodivir","description":"","frontmatter":{"layout":"paper","title":"Comprehensive profiling of mutations to influenza virus PB2 that confer resistance to the cap-binding inhibitor pimodivir","date":"2021-06-22","authors":["Shirleen YQ Soh","Keara D Malone","Rachel T Eguia","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v13071196","link":"https://www.mdpi.com/1999-4915/13/7/1196","image":"/assets/papers/2021_soh.png","keywords":["Influenza","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2021_soh.md","filePath":"papers/2021_soh.md"}'),o={name:"papers/2021_soh.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Antivirals are used not only in the current treatment of influenza but are also stockpiled as a first line of defense against novel influenza strains for which vaccines have yet to be developed. Identifying drug resistance mutations can guide the clinical deployment of the antiviral and can additionally define the mechanisms of drug action and drug resistance. Pimodivir is a first-in-class inhibitor of the polymerase basic protein 2 (PB2) subunit of the influenza A virus polymerase complex. A number of resistance mutations have previously been identified in treated patients or cell culture. Here, we generate a complete map of the effect of all single-amino-acid mutations to an avian PB2 on resistance to pimodivir. We identified both known and novel resistance mutations not only in the previously implicated cap-binding and mid-link domains, but also in the N-terminal domain. Our complete map of pimodivir resistance thus enables the evaluation of whether new viral strains contain mutations that will confer pimodivir resistance.",-1),l=[s,r];function c(d,p,h,m,u,f){return a(),t("div",null,l)}const b=i(o,[["render",c]]);export{_ as __pageData,b as default}; diff --git a/assets/papers_2021_starr_b.md.BY0zp4gH.js b/assets/papers_2021_starr_b.md.BDv6UmMj.js similarity index 94% rename from assets/papers_2021_starr_b.md.BY0zp4gH.js rename to assets/papers_2021_starr_b.md.BDv6UmMj.js index 4ccd3c5..b9e6416 100644 --- a/assets/papers_2021_starr_b.md.BY0zp4gH.js +++ b/assets/papers_2021_starr_b.md.BDv6UmMj.js @@ -1 +1 @@ -import{_ as t,c as a,o,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const f=JSON.parse('{"title":"Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016","description":"","frontmatter":{"layout":"paper","title":"Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016","date":"2021-04-20","authors":["Tyler N Starr","Allison J Greaney","Adam S Dingens","Jesse D Bloom"],"journal":"Cell Reports Medicine","doi":"10.1016/j.xcrm.2021.100255","link":"https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(21)00071-9.pdf","image":"/assets/papers/2021_starr_b.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2021_starr_b.md","filePath":"papers/2021_starr_b.md"}'),n={name:"papers/2021_starr_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Monoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for coronavirus disease 2019 (COVID-19). However, ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can render monoclonal antibodies ineffective. Here, we completely map all of the mutations to the SARS-CoV-2 spike receptor-binding domain (RBD) that escape binding by a leading monoclonal antibody, LY-CoV555, and its cocktail combination with LY-CoV016. Individual mutations that escape binding by each antibody are combined in the circulating B.1.351 and P.1 SARS-CoV-2 lineages (E484K escapes LY-CoV555, K417N/T escapes LY-CoV016). In addition, the L452R mutation in the B.1.429 lineage escapes LY-CoV555. Furthermore, we identify single amino acid changes that escape the combined LY-CoV555+LY-CoV016 cocktail. We suggest that future efforts diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to the antigenic evolution of SARS-CoV-2.",-1),c=[s,r];function l(d,p,m,h,b,u){return o(),a("div",null,c)}const C=t(n,[["render",l]]);export{f as __pageData,C as default}; +import{_ as t,c as a,o,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const f=JSON.parse('{"title":"Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016","description":"","frontmatter":{"layout":"paper","title":"Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016","date":"2021-04-20","authors":["Tyler N Starr","Allison J Greaney","Adam S Dingens","Jesse D Bloom"],"journal":"Cell Reports Medicine","doi":"10.1016/j.xcrm.2021.100255","link":"https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(21)00071-9.pdf","image":"/assets/papers/2021_starr_b.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2021_starr_b.md","filePath":"papers/2021_starr_b.md"}'),n={name:"papers/2021_starr_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Monoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for coronavirus disease 2019 (COVID-19). However, ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can render monoclonal antibodies ineffective. Here, we completely map all of the mutations to the SARS-CoV-2 spike receptor-binding domain (RBD) that escape binding by a leading monoclonal antibody, LY-CoV555, and its cocktail combination with LY-CoV016. Individual mutations that escape binding by each antibody are combined in the circulating B.1.351 and P.1 SARS-CoV-2 lineages (E484K escapes LY-CoV555, K417N/T escapes LY-CoV016). In addition, the L452R mutation in the B.1.429 lineage escapes LY-CoV555. Furthermore, we identify single amino acid changes that escape the combined LY-CoV555+LY-CoV016 cocktail. We suggest that future efforts diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to the antigenic evolution of SARS-CoV-2.",-1),c=[s,r];function l(d,p,m,h,b,u){return o(),a("div",null,c)}const C=t(n,[["render",l]]);export{f as __pageData,C as default}; diff --git a/assets/papers_2021_starr_b.md.BY0zp4gH.lean.js b/assets/papers_2021_starr_b.md.BDv6UmMj.lean.js similarity index 94% rename from assets/papers_2021_starr_b.md.BY0zp4gH.lean.js rename to assets/papers_2021_starr_b.md.BDv6UmMj.lean.js index 4ccd3c5..b9e6416 100644 --- a/assets/papers_2021_starr_b.md.BY0zp4gH.lean.js +++ b/assets/papers_2021_starr_b.md.BDv6UmMj.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const f=JSON.parse('{"title":"Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016","description":"","frontmatter":{"layout":"paper","title":"Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016","date":"2021-04-20","authors":["Tyler N Starr","Allison J Greaney","Adam S Dingens","Jesse D Bloom"],"journal":"Cell Reports Medicine","doi":"10.1016/j.xcrm.2021.100255","link":"https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(21)00071-9.pdf","image":"/assets/papers/2021_starr_b.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2021_starr_b.md","filePath":"papers/2021_starr_b.md"}'),n={name:"papers/2021_starr_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Monoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for coronavirus disease 2019 (COVID-19). However, ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can render monoclonal antibodies ineffective. Here, we completely map all of the mutations to the SARS-CoV-2 spike receptor-binding domain (RBD) that escape binding by a leading monoclonal antibody, LY-CoV555, and its cocktail combination with LY-CoV016. Individual mutations that escape binding by each antibody are combined in the circulating B.1.351 and P.1 SARS-CoV-2 lineages (E484K escapes LY-CoV555, K417N/T escapes LY-CoV016). In addition, the L452R mutation in the B.1.429 lineage escapes LY-CoV555. Furthermore, we identify single amino acid changes that escape the combined LY-CoV555+LY-CoV016 cocktail. We suggest that future efforts diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to the antigenic evolution of SARS-CoV-2.",-1),c=[s,r];function l(d,p,m,h,b,u){return o(),a("div",null,c)}const C=t(n,[["render",l]]);export{f as __pageData,C as default}; +import{_ as t,c as a,o,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const f=JSON.parse('{"title":"Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016","description":"","frontmatter":{"layout":"paper","title":"Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016","date":"2021-04-20","authors":["Tyler N Starr","Allison J Greaney","Adam S Dingens","Jesse D Bloom"],"journal":"Cell Reports Medicine","doi":"10.1016/j.xcrm.2021.100255","link":"https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(21)00071-9.pdf","image":"/assets/papers/2021_starr_b.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2021_starr_b.md","filePath":"papers/2021_starr_b.md"}'),n={name:"papers/2021_starr_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Monoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for coronavirus disease 2019 (COVID-19). However, ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can render monoclonal antibodies ineffective. Here, we completely map all of the mutations to the SARS-CoV-2 spike receptor-binding domain (RBD) that escape binding by a leading monoclonal antibody, LY-CoV555, and its cocktail combination with LY-CoV016. Individual mutations that escape binding by each antibody are combined in the circulating B.1.351 and P.1 SARS-CoV-2 lineages (E484K escapes LY-CoV555, K417N/T escapes LY-CoV016). In addition, the L452R mutation in the B.1.429 lineage escapes LY-CoV555. Furthermore, we identify single amino acid changes that escape the combined LY-CoV555+LY-CoV016 cocktail. We suggest that future efforts diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to the antigenic evolution of SARS-CoV-2.",-1),c=[s,r];function l(d,p,m,h,b,u){return o(),a("div",null,c)}const C=t(n,[["render",l]]);export{f as __pageData,C as default}; diff --git a/assets/papers_2021_starr_greaney.md.C_gmvhw7.js b/assets/papers_2021_starr_greaney.md.IB3VJQQN.js similarity index 96% rename from assets/papers_2021_starr_greaney.md.C_gmvhw7.js rename to assets/papers_2021_starr_greaney.md.IB3VJQQN.js index 7aab4be..9be0d81 100644 --- a/assets/papers_2021_starr_greaney.md.C_gmvhw7.js +++ b/assets/papers_2021_starr_greaney.md.IB3VJQQN.js @@ -1 +1 @@ -import{_ as a,c as t,o as i,b as e,d as s}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Prospective mapping of viral mutations that escape antibodies used to treat COVID-19","description":"","frontmatter":{"layout":"paper","title":"Prospective mapping of viral mutations that escape antibodies used to treat COVID-19","date":"2021-02-19","authors":["Tyler N Starr*","Allison J Greaney*","Amin Addetia","William W Hannon","Manish C Choudhary","Adam S Dingens","Jonathan Z Li","Jesse D Bloom"],"journal":"Science","doi":"10.1126/science.abf9302","link":"https://www.science.org/doi/full/10.1126/science.abf9302","image":"/assets/papers/2021_starr_greaney.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2021_starr_greaney.md","filePath":"papers/2021_starr_greaney.md"}'),n={name:"papers/2021_starr_greaney.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Antibodies are a potential therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to the receptor binding domain (RBD) of SARS-CoV-2 affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies, REGN10933 and REGN10987, targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2 and during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. These complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.",-1),c=[r,o];function l(d,p,h,m,u,_){return i(),t("div",null,c)}const b=a(n,[["render",l]]);export{g as __pageData,b as default}; +import{_ as a,c as t,o as i,b as e,d as s}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Prospective mapping of viral mutations that escape antibodies used to treat COVID-19","description":"","frontmatter":{"layout":"paper","title":"Prospective mapping of viral mutations that escape antibodies used to treat COVID-19","date":"2021-02-19","authors":["Tyler N Starr*","Allison J Greaney*","Amin Addetia","William W Hannon","Manish C Choudhary","Adam S Dingens","Jonathan Z Li","Jesse D Bloom"],"journal":"Science","doi":"10.1126/science.abf9302","link":"https://www.science.org/doi/full/10.1126/science.abf9302","image":"/assets/papers/2021_starr_greaney.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2021_starr_greaney.md","filePath":"papers/2021_starr_greaney.md"}'),n={name:"papers/2021_starr_greaney.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Antibodies are a potential therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to the receptor binding domain (RBD) of SARS-CoV-2 affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies, REGN10933 and REGN10987, targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2 and during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. These complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.",-1),c=[r,o];function l(d,p,h,m,u,_){return i(),t("div",null,c)}const b=a(n,[["render",l]]);export{g as __pageData,b as default}; diff --git a/assets/papers_2021_starr_greaney.md.C_gmvhw7.lean.js b/assets/papers_2021_starr_greaney.md.IB3VJQQN.lean.js similarity index 96% rename from assets/papers_2021_starr_greaney.md.C_gmvhw7.lean.js rename to assets/papers_2021_starr_greaney.md.IB3VJQQN.lean.js index 7aab4be..9be0d81 100644 --- a/assets/papers_2021_starr_greaney.md.C_gmvhw7.lean.js +++ b/assets/papers_2021_starr_greaney.md.IB3VJQQN.lean.js @@ -1 +1 @@ -import{_ as a,c as t,o as i,b as e,d as s}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Prospective mapping of viral mutations that escape antibodies used to treat COVID-19","description":"","frontmatter":{"layout":"paper","title":"Prospective mapping of viral mutations that escape antibodies used to treat COVID-19","date":"2021-02-19","authors":["Tyler N Starr*","Allison J Greaney*","Amin Addetia","William W Hannon","Manish C Choudhary","Adam S Dingens","Jonathan Z Li","Jesse D Bloom"],"journal":"Science","doi":"10.1126/science.abf9302","link":"https://www.science.org/doi/full/10.1126/science.abf9302","image":"/assets/papers/2021_starr_greaney.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2021_starr_greaney.md","filePath":"papers/2021_starr_greaney.md"}'),n={name:"papers/2021_starr_greaney.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Antibodies are a potential therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to the receptor binding domain (RBD) of SARS-CoV-2 affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies, REGN10933 and REGN10987, targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2 and during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. These complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.",-1),c=[r,o];function l(d,p,h,m,u,_){return i(),t("div",null,c)}const b=a(n,[["render",l]]);export{g as __pageData,b as default}; +import{_ as a,c as t,o as i,b as e,d as s}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Prospective mapping of viral mutations that escape antibodies used to treat COVID-19","description":"","frontmatter":{"layout":"paper","title":"Prospective mapping of viral mutations that escape antibodies used to treat COVID-19","date":"2021-02-19","authors":["Tyler N Starr*","Allison J Greaney*","Amin Addetia","William W Hannon","Manish C Choudhary","Adam S Dingens","Jonathan Z Li","Jesse D Bloom"],"journal":"Science","doi":"10.1126/science.abf9302","link":"https://www.science.org/doi/full/10.1126/science.abf9302","image":"/assets/papers/2021_starr_greaney.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2021_starr_greaney.md","filePath":"papers/2021_starr_greaney.md"}'),n={name:"papers/2021_starr_greaney.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Antibodies are a potential therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to the receptor binding domain (RBD) of SARS-CoV-2 affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies, REGN10933 and REGN10987, targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2 and during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. These complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.",-1),c=[r,o];function l(d,p,h,m,u,_){return i(),t("div",null,c)}const b=a(n,[["render",l]]);export{g as __pageData,b as default}; diff --git a/assets/papers_2021_starr_greaney_a.md.DF69-x2E.js b/assets/papers_2021_starr_greaney_a.md.CMhFAqkF.js similarity index 98% rename from assets/papers_2021_starr_greaney_a.md.DF69-x2E.js rename to assets/papers_2021_starr_greaney_a.md.CMhFAqkF.js index ed5e70f..ed0072d 100644 --- a/assets/papers_2021_starr_greaney_a.md.DF69-x2E.js +++ b/assets/papers_2021_starr_greaney_a.md.CMhFAqkF.js @@ -1 +1 @@ -import{_ as a,c as t,o as i,b as e,d as r}from"./chunks/framework.BqSDeblO.js";const m=JSON.parse('{"title":"SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape","description":"","frontmatter":{"layout":"paper","title":"SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape","date":"2021-09-02","authors":["Tyler N Starr","Nadine Czudnochowski","Zhuoming Liu","Fabrizia Zatta","Young-Jun Park","Amin Addetia","Dora Pinto","Martina Beltramello","Patrick Hernandez","Allison J Greaney","Roberta Marzi","William G Glass","Ivy Zhang","Adam S Dingens","John E Bowen","M Alejandra Tortorici","Alexandra C Walls","Jason A Wojcechowskyj","Anna De Marco","Laura E Rosen","Jiayi Zhou","Martin Montiel-Ruiz","Hannah Kaiser","Josh R Dillen","Heather Tucker","Jessica Bassi","Chiara Silacci-Fregni","Michael P Housley","Julia di Iulio","Gloria Lombardo","Maria Agostini","Nicole Sprugasci","Katja Culap","Stefano Jaconi","Marcel Meury","Exequiel Dellota Jr","Rana Abdelnabi","Shi-Yan Caroline Foo","Elisabetta Cameroni","Spencer Stumpf","Tristan I Croll","Jay C Nix","Colin Havenar-Daughton","Luca Piccoli","Fabio Benigni","Johan Neyts","Amalio Telenti","Florian A Lempp","Matteo S Pizzuto","John D Chodera","Christy M Hebner","Herbert W Virgin","Sean PJ Whelan","David Veesler","Davide Corti","Jesse D Bloom","Gyorgy Snell"],"journal":"Nature","doi":"10.1038/s41586-021-03807-6","link":"https://www.nature.com/articles/s41586-021-03807-6","image":"/assets/papers/2021_starr_greaney_a.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2021_starr_greaney_a.md","filePath":"papers/2021_starr_greaney_a.md"}'),n={name:"papers/2021_starr_greaney_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape, have activity against diverse sarbecoviruses, and be highly protective through viral neutralization and effector functions. Understanding how these properties relate to each other and vary across epitopes would aid the development of therapeutic antibodies and guide vaccine design. Here we comprehensively characterize escape, breadth and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD). Despite a trade-off between in vitro neutralization potency and breadth of sarbecovirus binding, we identify neutralizing antibodies with exceptional sarbecovirus breadth and a corresponding resistance to SARS-CoV-2 escape. One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a cryptic epitope and prophylactically protects hamsters from viral challenge. Antibodies that target the angiotensin-converting enzyme 2 (ACE2) receptor-binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency. Nevertheless, we also characterize a potent RBM antibody (S2E128) with breadth across sarbecoviruses related to SARS-CoV-2 and a high barrier to viral escape. These data highlight principles underlying variation in escape, breadth and potency among antibodies that target the RBD, and identify epitopes and features to prioritize for therapeutic development against the current and potential future pandemics.",-1),c=[o,s];function l(d,h,p,u,b,g){return i(),t("div",null,c)}const _=a(n,[["render",l]]);export{m as __pageData,_ as default}; +import{_ as a,c as t,o as i,b as e,d as r}from"./chunks/framework.D4bY2S_W.js";const m=JSON.parse('{"title":"SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape","description":"","frontmatter":{"layout":"paper","title":"SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape","date":"2021-09-02","authors":["Tyler N Starr","Nadine Czudnochowski","Zhuoming Liu","Fabrizia Zatta","Young-Jun Park","Amin Addetia","Dora Pinto","Martina Beltramello","Patrick Hernandez","Allison J Greaney","Roberta Marzi","William G Glass","Ivy Zhang","Adam S Dingens","John E Bowen","M Alejandra Tortorici","Alexandra C Walls","Jason A Wojcechowskyj","Anna De Marco","Laura E Rosen","Jiayi Zhou","Martin Montiel-Ruiz","Hannah Kaiser","Josh R Dillen","Heather Tucker","Jessica Bassi","Chiara Silacci-Fregni","Michael P Housley","Julia di Iulio","Gloria Lombardo","Maria Agostini","Nicole Sprugasci","Katja Culap","Stefano Jaconi","Marcel Meury","Exequiel Dellota Jr","Rana Abdelnabi","Shi-Yan Caroline Foo","Elisabetta Cameroni","Spencer Stumpf","Tristan I Croll","Jay C Nix","Colin Havenar-Daughton","Luca Piccoli","Fabio Benigni","Johan Neyts","Amalio Telenti","Florian A Lempp","Matteo S Pizzuto","John D Chodera","Christy M Hebner","Herbert W Virgin","Sean PJ Whelan","David Veesler","Davide Corti","Jesse D Bloom","Gyorgy Snell"],"journal":"Nature","doi":"10.1038/s41586-021-03807-6","link":"https://www.nature.com/articles/s41586-021-03807-6","image":"/assets/papers/2021_starr_greaney_a.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2021_starr_greaney_a.md","filePath":"papers/2021_starr_greaney_a.md"}'),n={name:"papers/2021_starr_greaney_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape, have activity against diverse sarbecoviruses, and be highly protective through viral neutralization and effector functions. Understanding how these properties relate to each other and vary across epitopes would aid the development of therapeutic antibodies and guide vaccine design. Here we comprehensively characterize escape, breadth and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD). Despite a trade-off between in vitro neutralization potency and breadth of sarbecovirus binding, we identify neutralizing antibodies with exceptional sarbecovirus breadth and a corresponding resistance to SARS-CoV-2 escape. One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a cryptic epitope and prophylactically protects hamsters from viral challenge. Antibodies that target the angiotensin-converting enzyme 2 (ACE2) receptor-binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency. Nevertheless, we also characterize a potent RBM antibody (S2E128) with breadth across sarbecoviruses related to SARS-CoV-2 and a high barrier to viral escape. These data highlight principles underlying variation in escape, breadth and potency among antibodies that target the RBD, and identify epitopes and features to prioritize for therapeutic development against the current and potential future pandemics.",-1),c=[o,s];function l(d,h,p,u,b,g){return i(),t("div",null,c)}const _=a(n,[["render",l]]);export{m as __pageData,_ as default}; diff --git a/assets/papers_2021_starr_greaney_a.md.DF69-x2E.lean.js b/assets/papers_2021_starr_greaney_a.md.CMhFAqkF.lean.js similarity index 98% rename from assets/papers_2021_starr_greaney_a.md.DF69-x2E.lean.js rename to assets/papers_2021_starr_greaney_a.md.CMhFAqkF.lean.js index ed5e70f..ed0072d 100644 --- a/assets/papers_2021_starr_greaney_a.md.DF69-x2E.lean.js +++ b/assets/papers_2021_starr_greaney_a.md.CMhFAqkF.lean.js @@ -1 +1 @@ -import{_ as a,c as t,o as i,b as e,d as r}from"./chunks/framework.BqSDeblO.js";const m=JSON.parse('{"title":"SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape","description":"","frontmatter":{"layout":"paper","title":"SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape","date":"2021-09-02","authors":["Tyler N Starr","Nadine Czudnochowski","Zhuoming Liu","Fabrizia Zatta","Young-Jun Park","Amin Addetia","Dora Pinto","Martina Beltramello","Patrick Hernandez","Allison J Greaney","Roberta Marzi","William G Glass","Ivy Zhang","Adam S Dingens","John E Bowen","M Alejandra Tortorici","Alexandra C Walls","Jason A Wojcechowskyj","Anna De Marco","Laura E Rosen","Jiayi Zhou","Martin Montiel-Ruiz","Hannah Kaiser","Josh R Dillen","Heather Tucker","Jessica Bassi","Chiara Silacci-Fregni","Michael P Housley","Julia di Iulio","Gloria Lombardo","Maria Agostini","Nicole Sprugasci","Katja Culap","Stefano Jaconi","Marcel Meury","Exequiel Dellota Jr","Rana Abdelnabi","Shi-Yan Caroline Foo","Elisabetta Cameroni","Spencer Stumpf","Tristan I Croll","Jay C Nix","Colin Havenar-Daughton","Luca Piccoli","Fabio Benigni","Johan Neyts","Amalio Telenti","Florian A Lempp","Matteo S Pizzuto","John D Chodera","Christy M Hebner","Herbert W Virgin","Sean PJ Whelan","David Veesler","Davide Corti","Jesse D Bloom","Gyorgy Snell"],"journal":"Nature","doi":"10.1038/s41586-021-03807-6","link":"https://www.nature.com/articles/s41586-021-03807-6","image":"/assets/papers/2021_starr_greaney_a.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2021_starr_greaney_a.md","filePath":"papers/2021_starr_greaney_a.md"}'),n={name:"papers/2021_starr_greaney_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape, have activity against diverse sarbecoviruses, and be highly protective through viral neutralization and effector functions. Understanding how these properties relate to each other and vary across epitopes would aid the development of therapeutic antibodies and guide vaccine design. Here we comprehensively characterize escape, breadth and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD). Despite a trade-off between in vitro neutralization potency and breadth of sarbecovirus binding, we identify neutralizing antibodies with exceptional sarbecovirus breadth and a corresponding resistance to SARS-CoV-2 escape. One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a cryptic epitope and prophylactically protects hamsters from viral challenge. Antibodies that target the angiotensin-converting enzyme 2 (ACE2) receptor-binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency. Nevertheless, we also characterize a potent RBM antibody (S2E128) with breadth across sarbecoviruses related to SARS-CoV-2 and a high barrier to viral escape. These data highlight principles underlying variation in escape, breadth and potency among antibodies that target the RBD, and identify epitopes and features to prioritize for therapeutic development against the current and potential future pandemics.",-1),c=[o,s];function l(d,h,p,u,b,g){return i(),t("div",null,c)}const _=a(n,[["render",l]]);export{m as __pageData,_ as default}; +import{_ as a,c as t,o as i,b as e,d as r}from"./chunks/framework.D4bY2S_W.js";const m=JSON.parse('{"title":"SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape","description":"","frontmatter":{"layout":"paper","title":"SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape","date":"2021-09-02","authors":["Tyler N Starr","Nadine Czudnochowski","Zhuoming Liu","Fabrizia Zatta","Young-Jun Park","Amin Addetia","Dora Pinto","Martina Beltramello","Patrick Hernandez","Allison J Greaney","Roberta Marzi","William G Glass","Ivy Zhang","Adam S Dingens","John E Bowen","M Alejandra Tortorici","Alexandra C Walls","Jason A Wojcechowskyj","Anna De Marco","Laura E Rosen","Jiayi Zhou","Martin Montiel-Ruiz","Hannah Kaiser","Josh R Dillen","Heather Tucker","Jessica Bassi","Chiara Silacci-Fregni","Michael P Housley","Julia di Iulio","Gloria Lombardo","Maria Agostini","Nicole Sprugasci","Katja Culap","Stefano Jaconi","Marcel Meury","Exequiel Dellota Jr","Rana Abdelnabi","Shi-Yan Caroline Foo","Elisabetta Cameroni","Spencer Stumpf","Tristan I Croll","Jay C Nix","Colin Havenar-Daughton","Luca Piccoli","Fabio Benigni","Johan Neyts","Amalio Telenti","Florian A Lempp","Matteo S Pizzuto","John D Chodera","Christy M Hebner","Herbert W Virgin","Sean PJ Whelan","David Veesler","Davide Corti","Jesse D Bloom","Gyorgy Snell"],"journal":"Nature","doi":"10.1038/s41586-021-03807-6","link":"https://www.nature.com/articles/s41586-021-03807-6","image":"/assets/papers/2021_starr_greaney_a.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2021_starr_greaney_a.md","filePath":"papers/2021_starr_greaney_a.md"}'),n={name:"papers/2021_starr_greaney_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape, have activity against diverse sarbecoviruses, and be highly protective through viral neutralization and effector functions. Understanding how these properties relate to each other and vary across epitopes would aid the development of therapeutic antibodies and guide vaccine design. Here we comprehensively characterize escape, breadth and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD). Despite a trade-off between in vitro neutralization potency and breadth of sarbecovirus binding, we identify neutralizing antibodies with exceptional sarbecovirus breadth and a corresponding resistance to SARS-CoV-2 escape. One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a cryptic epitope and prophylactically protects hamsters from viral challenge. Antibodies that target the angiotensin-converting enzyme 2 (ACE2) receptor-binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency. Nevertheless, we also characterize a potent RBM antibody (S2E128) with breadth across sarbecoviruses related to SARS-CoV-2 and a high barrier to viral escape. These data highlight principles underlying variation in escape, breadth and potency among antibodies that target the RBD, and identify epitopes and features to prioritize for therapeutic development against the current and potential future pandemics.",-1),c=[o,s];function l(d,h,p,u,b,g){return i(),t("div",null,c)}const _=a(n,[["render",l]]);export{m as __pageData,_ as default}; diff --git a/assets/papers_2022_farrell.md.BgwoSDFF.js b/assets/papers_2022_farrell.md.JaYpeG8h.js similarity index 97% rename from assets/papers_2022_farrell.md.BgwoSDFF.js rename to assets/papers_2022_farrell.md.JaYpeG8h.js index 5065a71..16f01a8 100644 --- a/assets/papers_2022_farrell.md.BgwoSDFF.js +++ b/assets/papers_2022_farrell.md.JaYpeG8h.js @@ -1 +1 @@ -import{_ as t,c as a,o as r,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Receptor-binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2","description":"","frontmatter":{"layout":"paper","title":"Receptor-binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2","date":"2022-09-16","authors":["Ariana Ghez Farrell*","Bernadeta Dadonaite*","Allison J Greaney","Rachel Eguia","Andrea N Loes","Nicholas M Franko","Jennifer Logue","Juan Manuel Carreño","Anass Abbad","Helen Y Chu","Kenneth A Matreyek","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v14092061","link":"https://www.mdpi.com/1999-4915/14/9/2061","image":"/assets/papers/2022_farrell.png","keywords":["SARS-CoV-2"]},"headers":[],"relativePath":"papers/2022_farrell.md","filePath":"papers/2022_farrell.md"}'),o={name:"papers/2022_farrell.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"Neutralization assays are experimental surrogates for the effectiveness of infection- or vaccine-elicited polyclonal antibodies and therapeutic monoclonal antibodies targeting SARS-CoV-2. However, the measured neutralization can depend on the details of the experimental assay. Here, we systematically assess how ACE2 expression in target cells affects neutralization by antibodies to different spike epitopes in lentivirus pseudovirus neutralization assays. For high ACE2-expressing target cells, receptor-binding domain (RBD) antibodies account for nearly all neutralizing activity in polyclonal human sera. However, for lower ACE2-expressing target cells, antibodies targeting regions outside the RBD make a larger (although still modest) contribution to serum neutralization. These serum-level results are mirrored for monoclonal antibodies: N-terminal domain (NTD) antibodies and RBD antibodies that do not compete for ACE2 binding incompletely neutralize on high ACE2-expressing target cells, but completely neutralize on cells with lower ACE2 expression. Our results show that the ACE2 expression level in the target cells is an important experimental variable, and that high ACE2 expression emphasizes the role of a subset of RBD-directed antibodies.",-1),l=[s,n];function c(d,p,h,u,m,f){return r(),a("div",null,l)}const _=t(o,[["render",c]]);export{b as __pageData,_ as default}; +import{_ as t,c as a,o as r,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Receptor-binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2","description":"","frontmatter":{"layout":"paper","title":"Receptor-binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2","date":"2022-09-16","authors":["Ariana Ghez Farrell*","Bernadeta Dadonaite*","Allison J Greaney","Rachel Eguia","Andrea N Loes","Nicholas M Franko","Jennifer Logue","Juan Manuel Carreño","Anass Abbad","Helen Y Chu","Kenneth A Matreyek","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v14092061","link":"https://www.mdpi.com/1999-4915/14/9/2061","image":"/assets/papers/2022_farrell.png","keywords":["SARS-CoV-2"]},"headers":[],"relativePath":"papers/2022_farrell.md","filePath":"papers/2022_farrell.md"}'),o={name:"papers/2022_farrell.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"Neutralization assays are experimental surrogates for the effectiveness of infection- or vaccine-elicited polyclonal antibodies and therapeutic monoclonal antibodies targeting SARS-CoV-2. However, the measured neutralization can depend on the details of the experimental assay. Here, we systematically assess how ACE2 expression in target cells affects neutralization by antibodies to different spike epitopes in lentivirus pseudovirus neutralization assays. For high ACE2-expressing target cells, receptor-binding domain (RBD) antibodies account for nearly all neutralizing activity in polyclonal human sera. However, for lower ACE2-expressing target cells, antibodies targeting regions outside the RBD make a larger (although still modest) contribution to serum neutralization. These serum-level results are mirrored for monoclonal antibodies: N-terminal domain (NTD) antibodies and RBD antibodies that do not compete for ACE2 binding incompletely neutralize on high ACE2-expressing target cells, but completely neutralize on cells with lower ACE2 expression. Our results show that the ACE2 expression level in the target cells is an important experimental variable, and that high ACE2 expression emphasizes the role of a subset of RBD-directed antibodies.",-1),l=[s,n];function c(d,p,h,u,m,f){return r(),a("div",null,l)}const _=t(o,[["render",c]]);export{b as __pageData,_ as default}; diff --git a/assets/papers_2022_farrell.md.BgwoSDFF.lean.js b/assets/papers_2022_farrell.md.JaYpeG8h.lean.js similarity index 97% rename from assets/papers_2022_farrell.md.BgwoSDFF.lean.js rename to assets/papers_2022_farrell.md.JaYpeG8h.lean.js index 5065a71..16f01a8 100644 --- a/assets/papers_2022_farrell.md.BgwoSDFF.lean.js +++ b/assets/papers_2022_farrell.md.JaYpeG8h.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as r,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Receptor-binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2","description":"","frontmatter":{"layout":"paper","title":"Receptor-binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2","date":"2022-09-16","authors":["Ariana Ghez Farrell*","Bernadeta Dadonaite*","Allison J Greaney","Rachel Eguia","Andrea N Loes","Nicholas M Franko","Jennifer Logue","Juan Manuel Carreño","Anass Abbad","Helen Y Chu","Kenneth A Matreyek","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v14092061","link":"https://www.mdpi.com/1999-4915/14/9/2061","image":"/assets/papers/2022_farrell.png","keywords":["SARS-CoV-2"]},"headers":[],"relativePath":"papers/2022_farrell.md","filePath":"papers/2022_farrell.md"}'),o={name:"papers/2022_farrell.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"Neutralization assays are experimental surrogates for the effectiveness of infection- or vaccine-elicited polyclonal antibodies and therapeutic monoclonal antibodies targeting SARS-CoV-2. However, the measured neutralization can depend on the details of the experimental assay. Here, we systematically assess how ACE2 expression in target cells affects neutralization by antibodies to different spike epitopes in lentivirus pseudovirus neutralization assays. For high ACE2-expressing target cells, receptor-binding domain (RBD) antibodies account for nearly all neutralizing activity in polyclonal human sera. However, for lower ACE2-expressing target cells, antibodies targeting regions outside the RBD make a larger (although still modest) contribution to serum neutralization. These serum-level results are mirrored for monoclonal antibodies: N-terminal domain (NTD) antibodies and RBD antibodies that do not compete for ACE2 binding incompletely neutralize on high ACE2-expressing target cells, but completely neutralize on cells with lower ACE2 expression. Our results show that the ACE2 expression level in the target cells is an important experimental variable, and that high ACE2 expression emphasizes the role of a subset of RBD-directed antibodies.",-1),l=[s,n];function c(d,p,h,u,m,f){return r(),a("div",null,l)}const _=t(o,[["render",c]]);export{b as __pageData,_ as default}; +import{_ as t,c as a,o as r,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Receptor-binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2","description":"","frontmatter":{"layout":"paper","title":"Receptor-binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2","date":"2022-09-16","authors":["Ariana Ghez Farrell*","Bernadeta Dadonaite*","Allison J Greaney","Rachel Eguia","Andrea N Loes","Nicholas M Franko","Jennifer Logue","Juan Manuel Carreño","Anass Abbad","Helen Y Chu","Kenneth A Matreyek","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v14092061","link":"https://www.mdpi.com/1999-4915/14/9/2061","image":"/assets/papers/2022_farrell.png","keywords":["SARS-CoV-2"]},"headers":[],"relativePath":"papers/2022_farrell.md","filePath":"papers/2022_farrell.md"}'),o={name:"papers/2022_farrell.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"Neutralization assays are experimental surrogates for the effectiveness of infection- or vaccine-elicited polyclonal antibodies and therapeutic monoclonal antibodies targeting SARS-CoV-2. However, the measured neutralization can depend on the details of the experimental assay. Here, we systematically assess how ACE2 expression in target cells affects neutralization by antibodies to different spike epitopes in lentivirus pseudovirus neutralization assays. For high ACE2-expressing target cells, receptor-binding domain (RBD) antibodies account for nearly all neutralizing activity in polyclonal human sera. However, for lower ACE2-expressing target cells, antibodies targeting regions outside the RBD make a larger (although still modest) contribution to serum neutralization. These serum-level results are mirrored for monoclonal antibodies: N-terminal domain (NTD) antibodies and RBD antibodies that do not compete for ACE2 binding incompletely neutralize on high ACE2-expressing target cells, but completely neutralize on cells with lower ACE2 expression. Our results show that the ACE2 expression level in the target cells is an important experimental variable, and that high ACE2 expression emphasizes the role of a subset of RBD-directed antibodies.",-1),l=[s,n];function c(d,p,h,u,m,f){return r(),a("div",null,l)}const _=t(o,[["render",c]]);export{b as __pageData,_ as default}; diff --git a/assets/papers_2022_gentles.md.8NXcHoF6.js b/assets/papers_2022_gentles.md.BP2KThjj.js similarity index 97% rename from assets/papers_2022_gentles.md.8NXcHoF6.js rename to assets/papers_2022_gentles.md.BP2KThjj.js index ef02904..0fcbf2c 100644 --- a/assets/papers_2022_gentles.md.8NXcHoF6.js +++ b/assets/papers_2022_gentles.md.BP2KThjj.js @@ -1 +1 @@ -import{_ as n,c as t,o as i,b as e,d as a}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time","description":"","frontmatter":{"layout":"paper","title":"Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time","date":"2022-01-25","authors":["Lauren E Gentles","Leanne Kehoe","Katharine HD Crawford","Kirsten Lacombe","Jane Dickerson","Caitlin Wolf","Joanna Yuan","Susanna Schuler","John T Watson","Sankan Nyanseor","Melissa Briggs-Hagen","Sharon Saydah","Claire M Midgley","Kimberly Pringle","Helen Chu","Jesse D Bloom","Janet A Englund"],"journal":"medRxiv","doi":"10.1101/2022.01.14.22269235","link":"https://www.medrxiv.org/content/10.1101/2022.01.14.22269235v1","image":"/assets/papers/2022_gentles.jpg","keywords":["SARS-CoV-2","Immunity"]},"headers":[],"relativePath":"papers/2022_gentles.md","filePath":"papers/2022_gentles.md"}'),o={name:"papers/2022_gentles.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits an antibody response that targets several viral proteins including spike (S) and nucleocapsid (N); S is the major target of neutralizing antibodies. Here, we assess levels of anti-N binding antibodies and anti-S neutralizing antibodies in unvaccinated children compared with unvaccinated older adults following infection. Specifically, we examine neutralization and anti-N binding by sera collected up to 52 weeks following SARS-CoV-2 infection in children and compare these to a cohort of adults, including older adults, most of whom had mild infections that did not require hospitalization. Neutralizing antibody titers were lower in children than adults early after infection, but by 6 months titers were similar between age groups. The neutralizing activity of the children’s sera decreased modestly from one to six months; a pattern that was not significantly different from that observed in adults. However, infection of children induced much lower levels of anti-N antibodies than in adults, and levels of these anti-N antibodies decreased more rapidly in children than in adults, including older adults. These results highlight age-related differences in the antibody responses to SARS-CoV-2 proteins and, as vaccines for children are introduced, may provide comparator data for the longevity of infection-elicited and vaccination-induced neutralizing antibody responses.",-1),d=[s,r];function l(c,h,u,f,p,m){return i(),t("div",null,d)}const y=n(o,[["render",l]]);export{b as __pageData,y as default}; +import{_ as n,c as t,o as i,b as e,d as a}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time","description":"","frontmatter":{"layout":"paper","title":"Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time","date":"2022-01-25","authors":["Lauren E Gentles","Leanne Kehoe","Katharine HD Crawford","Kirsten Lacombe","Jane Dickerson","Caitlin Wolf","Joanna Yuan","Susanna Schuler","John T Watson","Sankan Nyanseor","Melissa Briggs-Hagen","Sharon Saydah","Claire M Midgley","Kimberly Pringle","Helen Chu","Jesse D Bloom","Janet A Englund"],"journal":"medRxiv","doi":"10.1101/2022.01.14.22269235","link":"https://www.medrxiv.org/content/10.1101/2022.01.14.22269235v1","image":"/assets/papers/2022_gentles.jpg","keywords":["SARS-CoV-2","Immunity"]},"headers":[],"relativePath":"papers/2022_gentles.md","filePath":"papers/2022_gentles.md"}'),o={name:"papers/2022_gentles.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits an antibody response that targets several viral proteins including spike (S) and nucleocapsid (N); S is the major target of neutralizing antibodies. Here, we assess levels of anti-N binding antibodies and anti-S neutralizing antibodies in unvaccinated children compared with unvaccinated older adults following infection. Specifically, we examine neutralization and anti-N binding by sera collected up to 52 weeks following SARS-CoV-2 infection in children and compare these to a cohort of adults, including older adults, most of whom had mild infections that did not require hospitalization. Neutralizing antibody titers were lower in children than adults early after infection, but by 6 months titers were similar between age groups. The neutralizing activity of the children’s sera decreased modestly from one to six months; a pattern that was not significantly different from that observed in adults. However, infection of children induced much lower levels of anti-N antibodies than in adults, and levels of these anti-N antibodies decreased more rapidly in children than in adults, including older adults. These results highlight age-related differences in the antibody responses to SARS-CoV-2 proteins and, as vaccines for children are introduced, may provide comparator data for the longevity of infection-elicited and vaccination-induced neutralizing antibody responses.",-1),d=[s,r];function l(c,h,u,f,p,m){return i(),t("div",null,d)}const y=n(o,[["render",l]]);export{b as __pageData,y as default}; diff --git a/assets/papers_2022_gentles.md.8NXcHoF6.lean.js b/assets/papers_2022_gentles.md.BP2KThjj.lean.js similarity index 97% rename from assets/papers_2022_gentles.md.8NXcHoF6.lean.js rename to assets/papers_2022_gentles.md.BP2KThjj.lean.js index ef02904..0fcbf2c 100644 --- a/assets/papers_2022_gentles.md.8NXcHoF6.lean.js +++ b/assets/papers_2022_gentles.md.BP2KThjj.lean.js @@ -1 +1 @@ -import{_ as n,c as t,o as i,b as e,d as a}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time","description":"","frontmatter":{"layout":"paper","title":"Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time","date":"2022-01-25","authors":["Lauren E Gentles","Leanne Kehoe","Katharine HD Crawford","Kirsten Lacombe","Jane Dickerson","Caitlin Wolf","Joanna Yuan","Susanna Schuler","John T Watson","Sankan Nyanseor","Melissa Briggs-Hagen","Sharon Saydah","Claire M Midgley","Kimberly Pringle","Helen Chu","Jesse D Bloom","Janet A Englund"],"journal":"medRxiv","doi":"10.1101/2022.01.14.22269235","link":"https://www.medrxiv.org/content/10.1101/2022.01.14.22269235v1","image":"/assets/papers/2022_gentles.jpg","keywords":["SARS-CoV-2","Immunity"]},"headers":[],"relativePath":"papers/2022_gentles.md","filePath":"papers/2022_gentles.md"}'),o={name:"papers/2022_gentles.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits an antibody response that targets several viral proteins including spike (S) and nucleocapsid (N); S is the major target of neutralizing antibodies. Here, we assess levels of anti-N binding antibodies and anti-S neutralizing antibodies in unvaccinated children compared with unvaccinated older adults following infection. Specifically, we examine neutralization and anti-N binding by sera collected up to 52 weeks following SARS-CoV-2 infection in children and compare these to a cohort of adults, including older adults, most of whom had mild infections that did not require hospitalization. Neutralizing antibody titers were lower in children than adults early after infection, but by 6 months titers were similar between age groups. The neutralizing activity of the children’s sera decreased modestly from one to six months; a pattern that was not significantly different from that observed in adults. However, infection of children induced much lower levels of anti-N antibodies than in adults, and levels of these anti-N antibodies decreased more rapidly in children than in adults, including older adults. These results highlight age-related differences in the antibody responses to SARS-CoV-2 proteins and, as vaccines for children are introduced, may provide comparator data for the longevity of infection-elicited and vaccination-induced neutralizing antibody responses.",-1),d=[s,r];function l(c,h,u,f,p,m){return i(),t("div",null,d)}const y=n(o,[["render",l]]);export{b as __pageData,y as default}; +import{_ as n,c as t,o as i,b as e,d as a}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time","description":"","frontmatter":{"layout":"paper","title":"Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time","date":"2022-01-25","authors":["Lauren E Gentles","Leanne Kehoe","Katharine HD Crawford","Kirsten Lacombe","Jane Dickerson","Caitlin Wolf","Joanna Yuan","Susanna Schuler","John T Watson","Sankan Nyanseor","Melissa Briggs-Hagen","Sharon Saydah","Claire M Midgley","Kimberly Pringle","Helen Chu","Jesse D Bloom","Janet A Englund"],"journal":"medRxiv","doi":"10.1101/2022.01.14.22269235","link":"https://www.medrxiv.org/content/10.1101/2022.01.14.22269235v1","image":"/assets/papers/2022_gentles.jpg","keywords":["SARS-CoV-2","Immunity"]},"headers":[],"relativePath":"papers/2022_gentles.md","filePath":"papers/2022_gentles.md"}'),o={name:"papers/2022_gentles.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits an antibody response that targets several viral proteins including spike (S) and nucleocapsid (N); S is the major target of neutralizing antibodies. Here, we assess levels of anti-N binding antibodies and anti-S neutralizing antibodies in unvaccinated children compared with unvaccinated older adults following infection. Specifically, we examine neutralization and anti-N binding by sera collected up to 52 weeks following SARS-CoV-2 infection in children and compare these to a cohort of adults, including older adults, most of whom had mild infections that did not require hospitalization. Neutralizing antibody titers were lower in children than adults early after infection, but by 6 months titers were similar between age groups. The neutralizing activity of the children’s sera decreased modestly from one to six months; a pattern that was not significantly different from that observed in adults. However, infection of children induced much lower levels of anti-N antibodies than in adults, and levels of these anti-N antibodies decreased more rapidly in children than in adults, including older adults. These results highlight age-related differences in the antibody responses to SARS-CoV-2 proteins and, as vaccines for children are introduced, may provide comparator data for the longevity of infection-elicited and vaccination-induced neutralizing antibody responses.",-1),d=[s,r];function l(c,h,u,f,p,m){return i(),t("div",null,d)}const y=n(o,[["render",l]]);export{b as __pageData,y as default}; diff --git a/assets/papers_2022_greaney_a.md.qS2tR3O2.js b/assets/papers_2022_greaney_a.md.CiHEmU10.js similarity index 97% rename from assets/papers_2022_greaney_a.md.qS2tR3O2.js rename to assets/papers_2022_greaney_a.md.CiHEmU10.js index 71df739..3014cbf 100644 --- a/assets/papers_2022_greaney_a.md.qS2tR3O2.js +++ b/assets/papers_2022_greaney_a.md.CiHEmU10.js @@ -1 +1 @@ -import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const f=JSON.parse('{"title":"The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes","description":"","frontmatter":{"layout":"paper","title":"The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes","date":"2022-06-29","authors":["Allison J Greaney","Rachel T Eguia","Tyler N Starr","Khadija Khan","Nicholas Franko","Jennifer K Logue","Sandra M Lord","Cate Speake","Helen Y Chu","Alex Sigal","Jesse D Bloom"],"journal":"PLoS Pathogens","doi":"10.1371/journal.ppat.1010592","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010592","image":"/assets/papers/2022_greaney_a.png","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2022_greaney_a.md","filePath":"papers/2022_greaney_a.md"}'),o={name:"papers/2022_greaney_a.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Exposure histories to SARS-CoV-2 variants and vaccinations will shape the specificity of antibody responses. To understand the specificity of Delta-elicited antibody immunity, we characterize the polyclonal antibody response elicited by primary or mRNA vaccine-breakthrough Delta infections. Both types of infection elicit a neutralizing antibody response focused heavily on the receptor-binding domain (RBD). We use deep mutational scanning to show that mutations to the RBD’s class 1 and class 2 epitopes, including sites 417, 478, and 484–486 often reduce binding of these Delta-elicited antibodies. The anti-Delta antibody response is more similar to that elicited by early 2020 viruses than the Beta variant, with mutations to the class 1 and 2, but not class 3 epitopes, having the largest effects on polyclonal antibody binding. In addition, mutations to the class 1 epitope (e.g., K417N) tend to have larger effects on antibody binding and neutralization in the Delta spike than in the D614G spike, both for vaccine- and Delta-infection-elicited antibodies. These results help elucidate how the antigenic impacts of SARS-CoV-2 mutations depend on exposure history.",-1),l=[s,r];function c(d,p,h,u,y,g){return n(),t("div",null,l)}const m=a(o,[["render",c]]);export{f as __pageData,m as default}; +import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const f=JSON.parse('{"title":"The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes","description":"","frontmatter":{"layout":"paper","title":"The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes","date":"2022-06-29","authors":["Allison J Greaney","Rachel T Eguia","Tyler N Starr","Khadija Khan","Nicholas Franko","Jennifer K Logue","Sandra M Lord","Cate Speake","Helen Y Chu","Alex Sigal","Jesse D Bloom"],"journal":"PLoS Pathogens","doi":"10.1371/journal.ppat.1010592","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010592","image":"/assets/papers/2022_greaney_a.png","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2022_greaney_a.md","filePath":"papers/2022_greaney_a.md"}'),o={name:"papers/2022_greaney_a.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Exposure histories to SARS-CoV-2 variants and vaccinations will shape the specificity of antibody responses. To understand the specificity of Delta-elicited antibody immunity, we characterize the polyclonal antibody response elicited by primary or mRNA vaccine-breakthrough Delta infections. Both types of infection elicit a neutralizing antibody response focused heavily on the receptor-binding domain (RBD). We use deep mutational scanning to show that mutations to the RBD’s class 1 and class 2 epitopes, including sites 417, 478, and 484–486 often reduce binding of these Delta-elicited antibodies. The anti-Delta antibody response is more similar to that elicited by early 2020 viruses than the Beta variant, with mutations to the class 1 and 2, but not class 3 epitopes, having the largest effects on polyclonal antibody binding. In addition, mutations to the class 1 epitope (e.g., K417N) tend to have larger effects on antibody binding and neutralization in the Delta spike than in the D614G spike, both for vaccine- and Delta-infection-elicited antibodies. These results help elucidate how the antigenic impacts of SARS-CoV-2 mutations depend on exposure history.",-1),l=[s,r];function c(d,p,h,u,y,g){return n(),t("div",null,l)}const m=a(o,[["render",c]]);export{f as __pageData,m as default}; diff --git a/assets/papers_2022_greaney_a.md.qS2tR3O2.lean.js b/assets/papers_2022_greaney_a.md.CiHEmU10.lean.js similarity index 97% rename from assets/papers_2022_greaney_a.md.qS2tR3O2.lean.js rename to assets/papers_2022_greaney_a.md.CiHEmU10.lean.js index 71df739..3014cbf 100644 --- a/assets/papers_2022_greaney_a.md.qS2tR3O2.lean.js +++ b/assets/papers_2022_greaney_a.md.CiHEmU10.lean.js @@ -1 +1 @@ -import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const f=JSON.parse('{"title":"The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes","description":"","frontmatter":{"layout":"paper","title":"The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes","date":"2022-06-29","authors":["Allison J Greaney","Rachel T Eguia","Tyler N Starr","Khadija Khan","Nicholas Franko","Jennifer K Logue","Sandra M Lord","Cate Speake","Helen Y Chu","Alex Sigal","Jesse D Bloom"],"journal":"PLoS Pathogens","doi":"10.1371/journal.ppat.1010592","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010592","image":"/assets/papers/2022_greaney_a.png","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2022_greaney_a.md","filePath":"papers/2022_greaney_a.md"}'),o={name:"papers/2022_greaney_a.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Exposure histories to SARS-CoV-2 variants and vaccinations will shape the specificity of antibody responses. To understand the specificity of Delta-elicited antibody immunity, we characterize the polyclonal antibody response elicited by primary or mRNA vaccine-breakthrough Delta infections. Both types of infection elicit a neutralizing antibody response focused heavily on the receptor-binding domain (RBD). We use deep mutational scanning to show that mutations to the RBD’s class 1 and class 2 epitopes, including sites 417, 478, and 484–486 often reduce binding of these Delta-elicited antibodies. The anti-Delta antibody response is more similar to that elicited by early 2020 viruses than the Beta variant, with mutations to the class 1 and 2, but not class 3 epitopes, having the largest effects on polyclonal antibody binding. In addition, mutations to the class 1 epitope (e.g., K417N) tend to have larger effects on antibody binding and neutralization in the Delta spike than in the D614G spike, both for vaccine- and Delta-infection-elicited antibodies. These results help elucidate how the antigenic impacts of SARS-CoV-2 mutations depend on exposure history.",-1),l=[s,r];function c(d,p,h,u,y,g){return n(),t("div",null,l)}const m=a(o,[["render",c]]);export{f as __pageData,m as default}; +import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const f=JSON.parse('{"title":"The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes","description":"","frontmatter":{"layout":"paper","title":"The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes","date":"2022-06-29","authors":["Allison J Greaney","Rachel T Eguia","Tyler N Starr","Khadija Khan","Nicholas Franko","Jennifer K Logue","Sandra M Lord","Cate Speake","Helen Y Chu","Alex Sigal","Jesse D Bloom"],"journal":"PLoS Pathogens","doi":"10.1371/journal.ppat.1010592","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010592","image":"/assets/papers/2022_greaney_a.png","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2022_greaney_a.md","filePath":"papers/2022_greaney_a.md"}'),o={name:"papers/2022_greaney_a.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Exposure histories to SARS-CoV-2 variants and vaccinations will shape the specificity of antibody responses. To understand the specificity of Delta-elicited antibody immunity, we characterize the polyclonal antibody response elicited by primary or mRNA vaccine-breakthrough Delta infections. Both types of infection elicit a neutralizing antibody response focused heavily on the receptor-binding domain (RBD). We use deep mutational scanning to show that mutations to the RBD’s class 1 and class 2 epitopes, including sites 417, 478, and 484–486 often reduce binding of these Delta-elicited antibodies. The anti-Delta antibody response is more similar to that elicited by early 2020 viruses than the Beta variant, with mutations to the class 1 and 2, but not class 3 epitopes, having the largest effects on polyclonal antibody binding. In addition, mutations to the class 1 epitope (e.g., K417N) tend to have larger effects on antibody binding and neutralization in the Delta spike than in the D614G spike, both for vaccine- and Delta-infection-elicited antibodies. These results help elucidate how the antigenic impacts of SARS-CoV-2 mutations depend on exposure history.",-1),l=[s,r];function c(d,p,h,u,y,g){return n(),t("div",null,l)}const m=a(o,[["render",c]]);export{f as __pageData,m as default}; diff --git a/assets/papers_2022_greaney_b.md.CQtogWRb.js b/assets/papers_2022_greaney_b.md.DWzt8_d0.js similarity index 97% rename from assets/papers_2022_greaney_b.md.CQtogWRb.js rename to assets/papers_2022_greaney_b.md.DWzt8_d0.js index 62932bb..3586175 100644 --- a/assets/papers_2022_greaney_b.md.CQtogWRb.js +++ b/assets/papers_2022_greaney_b.md.DWzt8_d0.js @@ -1 +1 @@ -import{_ as a,c as i,o as t,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const f=JSON.parse('{"title":"A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy","description":"","frontmatter":{"layout":"paper","title":"A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy","date":"2022-02-08","authors":["Allison J Greaney","Tyler N Starr","Rachel T Eguia","Andrea N Loes","Khadija Khan","Farina Karim","Sandile Cele","John E Bowen","Jennifer K Logue","Davide Corti","David Veesler","Helen Y Chu","Alex Sigal","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1010248","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010248","image":"/assets/papers/2022_greaney_b.png","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2022_greaney_b.md","filePath":"papers/2022_greaney_b.md"}'),s={name:"papers/2022_greaney_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the “class 3” epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.",-1),l=[o,r];function c(d,h,p,u,m,b){return t(),i("div",null,l)}const _=a(s,[["render",c]]);export{f as __pageData,_ as default}; +import{_ as a,c as i,o as t,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const f=JSON.parse('{"title":"A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy","description":"","frontmatter":{"layout":"paper","title":"A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy","date":"2022-02-08","authors":["Allison J Greaney","Tyler N Starr","Rachel T Eguia","Andrea N Loes","Khadija Khan","Farina Karim","Sandile Cele","John E Bowen","Jennifer K Logue","Davide Corti","David Veesler","Helen Y Chu","Alex Sigal","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1010248","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010248","image":"/assets/papers/2022_greaney_b.png","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2022_greaney_b.md","filePath":"papers/2022_greaney_b.md"}'),s={name:"papers/2022_greaney_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the “class 3” epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.",-1),l=[o,r];function c(d,h,p,u,m,b){return t(),i("div",null,l)}const _=a(s,[["render",c]]);export{f as __pageData,_ as default}; diff --git a/assets/papers_2022_greaney_b.md.CQtogWRb.lean.js b/assets/papers_2022_greaney_b.md.DWzt8_d0.lean.js similarity index 97% rename from assets/papers_2022_greaney_b.md.CQtogWRb.lean.js rename to assets/papers_2022_greaney_b.md.DWzt8_d0.lean.js index 62932bb..3586175 100644 --- a/assets/papers_2022_greaney_b.md.CQtogWRb.lean.js +++ b/assets/papers_2022_greaney_b.md.DWzt8_d0.lean.js @@ -1 +1 @@ -import{_ as a,c as i,o as t,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const f=JSON.parse('{"title":"A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy","description":"","frontmatter":{"layout":"paper","title":"A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy","date":"2022-02-08","authors":["Allison J Greaney","Tyler N Starr","Rachel T Eguia","Andrea N Loes","Khadija Khan","Farina Karim","Sandile Cele","John E Bowen","Jennifer K Logue","Davide Corti","David Veesler","Helen Y Chu","Alex Sigal","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1010248","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010248","image":"/assets/papers/2022_greaney_b.png","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2022_greaney_b.md","filePath":"papers/2022_greaney_b.md"}'),s={name:"papers/2022_greaney_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the “class 3” epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.",-1),l=[o,r];function c(d,h,p,u,m,b){return t(),i("div",null,l)}const _=a(s,[["render",c]]);export{f as __pageData,_ as default}; +import{_ as a,c as i,o as t,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const f=JSON.parse('{"title":"A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy","description":"","frontmatter":{"layout":"paper","title":"A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy","date":"2022-02-08","authors":["Allison J Greaney","Tyler N Starr","Rachel T Eguia","Andrea N Loes","Khadija Khan","Farina Karim","Sandile Cele","John E Bowen","Jennifer K Logue","Davide Corti","David Veesler","Helen Y Chu","Alex Sigal","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1010248","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010248","image":"/assets/papers/2022_greaney_b.png","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2022_greaney_b.md","filePath":"papers/2022_greaney_b.md"}'),s={name:"papers/2022_greaney_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the “class 3” epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.",-1),l=[o,r];function c(d,h,p,u,m,b){return t(),i("div",null,l)}const _=a(s,[["render",c]]);export{f as __pageData,_ as default}; diff --git a/assets/papers_2022_greaney_c.md.BYB2eFpi.js b/assets/papers_2022_greaney_c.md.BtKGaOA7.js similarity index 95% rename from assets/papers_2022_greaney_c.md.BYB2eFpi.js rename to assets/papers_2022_greaney_c.md.BtKGaOA7.js index 6719703..2d34977 100644 --- a/assets/papers_2022_greaney_c.md.BYB2eFpi.js +++ b/assets/papers_2022_greaney_c.md.BtKGaOA7.js @@ -1 +1 @@ -import{_ as a,c as i,o,b as e,d as t}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain","description":"","frontmatter":{"layout":"paper","title":"An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain","date":"2022-01-01","authors":["Allison J Greaney","Tyler N Starr","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac021","link":"https://academic.oup.com/ve/article/8/1/veac021/6549895","image":"/assets/papers/2022_greaney_c.jpg","keywords":["SARS-CoV-2","Software tools","Immunity"]},"headers":[],"relativePath":"papers/2022_greaney_c.md","filePath":"papers/2022_greaney_c.md"}'),r={name:"papers/2022_greaney_c.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,[t("A key goal of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surveillance is to rapidly identify viral variants with mutations that reduce neutralization by polyclonal antibodies elicited by vaccination or infection. Unfortunately, direct experimental characterization of new viral variants lags their sequence-based identification. Here we help address this challenge by aggregating deep mutational scanning data into an ‘escape estimator’ that estimates the antigenic effects of arbitrary combinations of mutations to the virus’s spike receptor-binding domain. The estimator can be used to intuitively visualize how mutations impact polyclonal antibody recognition and score the expected antigenic effect of combinations of mutations. These scores correlate with neutralization assays performed on SARS-CoV-2 variants and emphasize the ominous antigenic properties of the recently described Omicron variant. An interactive version of the estimator is at "),e("a",{href:"https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/"),t(" (last accessed 11 March 2022), and we provide a Python module for batch processing. Currently the calculator uses primarily data for antibodies elicited by Wuhan-Hu-1-like vaccination or infection and so is expected to work best for calculating escape from such immunity for mutations relative to early SARS-CoV-2 strains.")],-1),c=[n,s];function l(d,p,m,h,u,f){return o(),i("div",null,c)}const y=a(r,[["render",l]]);export{b as __pageData,y as default}; +import{_ as a,c as i,o,b as e,d as t}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain","description":"","frontmatter":{"layout":"paper","title":"An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain","date":"2022-01-01","authors":["Allison J Greaney","Tyler N Starr","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac021","link":"https://academic.oup.com/ve/article/8/1/veac021/6549895","image":"/assets/papers/2022_greaney_c.jpg","keywords":["SARS-CoV-2","Software tools","Immunity"]},"headers":[],"relativePath":"papers/2022_greaney_c.md","filePath":"papers/2022_greaney_c.md"}'),r={name:"papers/2022_greaney_c.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,[t("A key goal of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surveillance is to rapidly identify viral variants with mutations that reduce neutralization by polyclonal antibodies elicited by vaccination or infection. Unfortunately, direct experimental characterization of new viral variants lags their sequence-based identification. Here we help address this challenge by aggregating deep mutational scanning data into an ‘escape estimator’ that estimates the antigenic effects of arbitrary combinations of mutations to the virus’s spike receptor-binding domain. The estimator can be used to intuitively visualize how mutations impact polyclonal antibody recognition and score the expected antigenic effect of combinations of mutations. These scores correlate with neutralization assays performed on SARS-CoV-2 variants and emphasize the ominous antigenic properties of the recently described Omicron variant. An interactive version of the estimator is at "),e("a",{href:"https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/"),t(" (last accessed 11 March 2022), and we provide a Python module for batch processing. Currently the calculator uses primarily data for antibodies elicited by Wuhan-Hu-1-like vaccination or infection and so is expected to work best for calculating escape from such immunity for mutations relative to early SARS-CoV-2 strains.")],-1),c=[n,s];function l(d,p,m,h,u,f){return o(),i("div",null,c)}const y=a(r,[["render",l]]);export{b as __pageData,y as default}; diff --git a/assets/papers_2022_greaney_c.md.BYB2eFpi.lean.js b/assets/papers_2022_greaney_c.md.BtKGaOA7.lean.js similarity index 95% rename from assets/papers_2022_greaney_c.md.BYB2eFpi.lean.js rename to assets/papers_2022_greaney_c.md.BtKGaOA7.lean.js index 6719703..2d34977 100644 --- a/assets/papers_2022_greaney_c.md.BYB2eFpi.lean.js +++ b/assets/papers_2022_greaney_c.md.BtKGaOA7.lean.js @@ -1 +1 @@ -import{_ as a,c as i,o,b as e,d as t}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain","description":"","frontmatter":{"layout":"paper","title":"An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain","date":"2022-01-01","authors":["Allison J Greaney","Tyler N Starr","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac021","link":"https://academic.oup.com/ve/article/8/1/veac021/6549895","image":"/assets/papers/2022_greaney_c.jpg","keywords":["SARS-CoV-2","Software tools","Immunity"]},"headers":[],"relativePath":"papers/2022_greaney_c.md","filePath":"papers/2022_greaney_c.md"}'),r={name:"papers/2022_greaney_c.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,[t("A key goal of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surveillance is to rapidly identify viral variants with mutations that reduce neutralization by polyclonal antibodies elicited by vaccination or infection. Unfortunately, direct experimental characterization of new viral variants lags their sequence-based identification. Here we help address this challenge by aggregating deep mutational scanning data into an ‘escape estimator’ that estimates the antigenic effects of arbitrary combinations of mutations to the virus’s spike receptor-binding domain. The estimator can be used to intuitively visualize how mutations impact polyclonal antibody recognition and score the expected antigenic effect of combinations of mutations. These scores correlate with neutralization assays performed on SARS-CoV-2 variants and emphasize the ominous antigenic properties of the recently described Omicron variant. An interactive version of the estimator is at "),e("a",{href:"https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/"),t(" (last accessed 11 March 2022), and we provide a Python module for batch processing. Currently the calculator uses primarily data for antibodies elicited by Wuhan-Hu-1-like vaccination or infection and so is expected to work best for calculating escape from such immunity for mutations relative to early SARS-CoV-2 strains.")],-1),c=[n,s];function l(d,p,m,h,u,f){return o(),i("div",null,c)}const y=a(r,[["render",l]]);export{b as __pageData,y as default}; +import{_ as a,c as i,o,b as e,d as t}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain","description":"","frontmatter":{"layout":"paper","title":"An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain","date":"2022-01-01","authors":["Allison J Greaney","Tyler N Starr","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac021","link":"https://academic.oup.com/ve/article/8/1/veac021/6549895","image":"/assets/papers/2022_greaney_c.jpg","keywords":["SARS-CoV-2","Software tools","Immunity"]},"headers":[],"relativePath":"papers/2022_greaney_c.md","filePath":"papers/2022_greaney_c.md"}'),r={name:"papers/2022_greaney_c.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,[t("A key goal of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surveillance is to rapidly identify viral variants with mutations that reduce neutralization by polyclonal antibodies elicited by vaccination or infection. Unfortunately, direct experimental characterization of new viral variants lags their sequence-based identification. Here we help address this challenge by aggregating deep mutational scanning data into an ‘escape estimator’ that estimates the antigenic effects of arbitrary combinations of mutations to the virus’s spike receptor-binding domain. The estimator can be used to intuitively visualize how mutations impact polyclonal antibody recognition and score the expected antigenic effect of combinations of mutations. These scores correlate with neutralization assays performed on SARS-CoV-2 variants and emphasize the ominous antigenic properties of the recently described Omicron variant. An interactive version of the estimator is at "),e("a",{href:"https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/"),t(" (last accessed 11 March 2022), and we provide a Python module for batch processing. Currently the calculator uses primarily data for antibodies elicited by Wuhan-Hu-1-like vaccination or infection and so is expected to work best for calculating escape from such immunity for mutations relative to early SARS-CoV-2 strains.")],-1),c=[n,s];function l(d,p,m,h,u,f){return o(),i("div",null,c)}const y=a(r,[["render",l]]);export{b as __pageData,y as default}; diff --git a/assets/papers_2022_hannon.md.4DnVJIyi.js b/assets/papers_2022_hannon.md.CmZdo8Lg.js similarity index 97% rename from assets/papers_2022_hannon.md.4DnVJIyi.js rename to assets/papers_2022_hannon.md.CmZdo8Lg.js index 7d5022f..94a9d67 100644 --- a/assets/papers_2022_hannon.md.4DnVJIyi.js +++ b/assets/papers_2022_hannon.md.CmZdo8Lg.js @@ -1 +1 @@ -import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat","description":"","frontmatter":{"layout":"paper","title":"Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat","date":"2022-07-01","authors":["William W Hannon","Pavitra Roychoudhury","Hong Xie","Lasata Shrestha","Amin Addetia","Keith R Jerome","Alexander L Greninger","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac052","link":"https://academic.oup.com/ve/article/8/2/veac052/6609212","image":"/assets/papers/2022_hannon.jpg","keywords":["SARS-CoV-2","Within-host evolution"]},"headers":[],"relativePath":"papers/2022_hannon.md","filePath":"papers/2022_hannon.md"}'),o={name:"papers/2022_hannon.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The long-term evolution of viruses is ultimately due to viral mutants that arise within infected individuals and transmit to other individuals. Here, we use deep sequencing to investigate the transmission of viral genetic variation among individuals during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak that infected the vast majority of crew members on a fishing boat. We deep-sequenced nasal swabs to characterize the within-host viral population of infected crew members, using experimental duplicates and strict computational filters to ensure accurate variant calling. We find that within-host viral diversity is low in infected crew members. The mutations that did fix in some crew members during the outbreak are not observed at detectable frequencies in any of the sampled crew members in which they are not fixed, suggesting that viral evolution involves occasional fixation of low-frequency mutations during transmission rather than persistent maintenance of within-host viral diversity. Overall, our results show that strong transmission bottlenecks dominate viral evolution even during a superspreading event with a very high attack rate.",-1),d=[r,s];function c(l,h,u,m,v,p){return i(),a("div",null,d)}const b=t(o,[["render",c]]);export{g as __pageData,b as default}; +import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat","description":"","frontmatter":{"layout":"paper","title":"Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat","date":"2022-07-01","authors":["William W Hannon","Pavitra Roychoudhury","Hong Xie","Lasata Shrestha","Amin Addetia","Keith R Jerome","Alexander L Greninger","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac052","link":"https://academic.oup.com/ve/article/8/2/veac052/6609212","image":"/assets/papers/2022_hannon.jpg","keywords":["SARS-CoV-2","Within-host evolution"]},"headers":[],"relativePath":"papers/2022_hannon.md","filePath":"papers/2022_hannon.md"}'),o={name:"papers/2022_hannon.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The long-term evolution of viruses is ultimately due to viral mutants that arise within infected individuals and transmit to other individuals. Here, we use deep sequencing to investigate the transmission of viral genetic variation among individuals during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak that infected the vast majority of crew members on a fishing boat. We deep-sequenced nasal swabs to characterize the within-host viral population of infected crew members, using experimental duplicates and strict computational filters to ensure accurate variant calling. We find that within-host viral diversity is low in infected crew members. The mutations that did fix in some crew members during the outbreak are not observed at detectable frequencies in any of the sampled crew members in which they are not fixed, suggesting that viral evolution involves occasional fixation of low-frequency mutations during transmission rather than persistent maintenance of within-host viral diversity. Overall, our results show that strong transmission bottlenecks dominate viral evolution even during a superspreading event with a very high attack rate.",-1),d=[r,s];function c(l,h,u,m,v,p){return i(),a("div",null,d)}const b=t(o,[["render",c]]);export{g as __pageData,b as default}; diff --git a/assets/papers_2022_hannon.md.4DnVJIyi.lean.js b/assets/papers_2022_hannon.md.CmZdo8Lg.lean.js similarity index 97% rename from assets/papers_2022_hannon.md.4DnVJIyi.lean.js rename to assets/papers_2022_hannon.md.CmZdo8Lg.lean.js index 7d5022f..94a9d67 100644 --- a/assets/papers_2022_hannon.md.4DnVJIyi.lean.js +++ b/assets/papers_2022_hannon.md.CmZdo8Lg.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat","description":"","frontmatter":{"layout":"paper","title":"Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat","date":"2022-07-01","authors":["William W Hannon","Pavitra Roychoudhury","Hong Xie","Lasata Shrestha","Amin Addetia","Keith R Jerome","Alexander L Greninger","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac052","link":"https://academic.oup.com/ve/article/8/2/veac052/6609212","image":"/assets/papers/2022_hannon.jpg","keywords":["SARS-CoV-2","Within-host evolution"]},"headers":[],"relativePath":"papers/2022_hannon.md","filePath":"papers/2022_hannon.md"}'),o={name:"papers/2022_hannon.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The long-term evolution of viruses is ultimately due to viral mutants that arise within infected individuals and transmit to other individuals. Here, we use deep sequencing to investigate the transmission of viral genetic variation among individuals during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak that infected the vast majority of crew members on a fishing boat. We deep-sequenced nasal swabs to characterize the within-host viral population of infected crew members, using experimental duplicates and strict computational filters to ensure accurate variant calling. We find that within-host viral diversity is low in infected crew members. The mutations that did fix in some crew members during the outbreak are not observed at detectable frequencies in any of the sampled crew members in which they are not fixed, suggesting that viral evolution involves occasional fixation of low-frequency mutations during transmission rather than persistent maintenance of within-host viral diversity. Overall, our results show that strong transmission bottlenecks dominate viral evolution even during a superspreading event with a very high attack rate.",-1),d=[r,s];function c(l,h,u,m,v,p){return i(),a("div",null,d)}const b=t(o,[["render",c]]);export{g as __pageData,b as default}; +import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat","description":"","frontmatter":{"layout":"paper","title":"Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat","date":"2022-07-01","authors":["William W Hannon","Pavitra Roychoudhury","Hong Xie","Lasata Shrestha","Amin Addetia","Keith R Jerome","Alexander L Greninger","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac052","link":"https://academic.oup.com/ve/article/8/2/veac052/6609212","image":"/assets/papers/2022_hannon.jpg","keywords":["SARS-CoV-2","Within-host evolution"]},"headers":[],"relativePath":"papers/2022_hannon.md","filePath":"papers/2022_hannon.md"}'),o={name:"papers/2022_hannon.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The long-term evolution of viruses is ultimately due to viral mutants that arise within infected individuals and transmit to other individuals. Here, we use deep sequencing to investigate the transmission of viral genetic variation among individuals during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak that infected the vast majority of crew members on a fishing boat. We deep-sequenced nasal swabs to characterize the within-host viral population of infected crew members, using experimental duplicates and strict computational filters to ensure accurate variant calling. We find that within-host viral diversity is low in infected crew members. The mutations that did fix in some crew members during the outbreak are not observed at detectable frequencies in any of the sampled crew members in which they are not fixed, suggesting that viral evolution involves occasional fixation of low-frequency mutations during transmission rather than persistent maintenance of within-host viral diversity. Overall, our results show that strong transmission bottlenecks dominate viral evolution even during a superspreading event with a very high attack rate.",-1),d=[r,s];function c(l,h,u,m,v,p){return i(),a("div",null,d)}const b=t(o,[["render",c]]);export{g as __pageData,b as default}; diff --git a/assets/papers_2022_starr_a.md.DHkPF2CP.js b/assets/papers_2022_starr_a.md.S2Zs3F-f.js similarity index 97% rename from assets/papers_2022_starr_a.md.DHkPF2CP.js rename to assets/papers_2022_starr_a.md.S2Zs3F-f.js index f5f1b67..a99970c 100644 --- a/assets/papers_2022_starr_a.md.DHkPF2CP.js +++ b/assets/papers_2022_starr_a.md.S2Zs3F-f.js @@ -1 +1 @@ -import{_ as a,c as s,o as t,b as e,d as r}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"ACE2 binding is an ancestral and evolvable trait of sarbecoviruses","description":"","frontmatter":{"layout":"paper","title":"ACE2 binding is an ancestral and evolvable trait of sarbecoviruses","date":"2022-03-31","authors":["Tyler N Starr","Samantha K Zepeda","Alexandra C Walls","Allison J Greaney","Sergey Alkhovsky","David Veesler","Jesse D Bloom"],"journal":"Nature","doi":"10.1038/s41586-022-04464-z","link":"https://www.nature.com/articles/s41586-022-04464-z","image":"/assets/papers/2022_starr_a.jpg","keywords":["Coronavirus","Phylogenetics","Yeast display"]},"headers":[],"relativePath":"papers/2022_starr_a.md","filePath":"papers/2022_starr_a.md"}'),o={name:"papers/2022_starr_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"Two different sarbecoviruses have caused major human outbreaks in the past two decades. Both of these sarbecoviruses, SARS-CoV-1 and SARS-CoV-2, engage ACE2 through the spike receptor-binding domain. However, binding to ACE2 orthologues of humans, bats and other species has been observed only sporadically among the broader diversity of bat sarbecoviruses. Here we use high-throughput assays to trace the evolutionary history of ACE2 binding across a diverse range of sarbecoviruses and ACE2 orthologues. We find that ACE2 binding is an ancestral trait of sarbecovirus receptor-binding domains that has subsequently been lost in some clades. Furthermore, we reveal that bat sarbecoviruses from outside Asia can bind to ACE2. Moreover, ACE2 binding is highly evolvable—for many sarbecovirus receptor-binding domains, there are single amino-acid mutations that enable binding to new ACE2 orthologues. However, the effects of individual mutations can differ considerably between viruses, as shown by the N501Y mutation, which enhances the human ACE2-binding affinity of several SARS-CoV-2 variants of concern but substantially decreases it for SARS-CoV-1. Our results point to the deep ancestral origin and evolutionary plasticity of ACE2 binding, broadening the range of sarbecoviruses that should be considered to have spillover potential.",-1),d=[n,i];function l(c,h,b,u,p,v){return t(),s("div",null,d)}const m=a(o,[["render",l]]);export{g as __pageData,m as default}; +import{_ as a,c as s,o as t,b as e,d as r}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"ACE2 binding is an ancestral and evolvable trait of sarbecoviruses","description":"","frontmatter":{"layout":"paper","title":"ACE2 binding is an ancestral and evolvable trait of sarbecoviruses","date":"2022-03-31","authors":["Tyler N Starr","Samantha K Zepeda","Alexandra C Walls","Allison J Greaney","Sergey Alkhovsky","David Veesler","Jesse D Bloom"],"journal":"Nature","doi":"10.1038/s41586-022-04464-z","link":"https://www.nature.com/articles/s41586-022-04464-z","image":"/assets/papers/2022_starr_a.jpg","keywords":["Coronavirus","Phylogenetics","Yeast display"]},"headers":[],"relativePath":"papers/2022_starr_a.md","filePath":"papers/2022_starr_a.md"}'),o={name:"papers/2022_starr_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"Two different sarbecoviruses have caused major human outbreaks in the past two decades. Both of these sarbecoviruses, SARS-CoV-1 and SARS-CoV-2, engage ACE2 through the spike receptor-binding domain. However, binding to ACE2 orthologues of humans, bats and other species has been observed only sporadically among the broader diversity of bat sarbecoviruses. Here we use high-throughput assays to trace the evolutionary history of ACE2 binding across a diverse range of sarbecoviruses and ACE2 orthologues. We find that ACE2 binding is an ancestral trait of sarbecovirus receptor-binding domains that has subsequently been lost in some clades. Furthermore, we reveal that bat sarbecoviruses from outside Asia can bind to ACE2. Moreover, ACE2 binding is highly evolvable—for many sarbecovirus receptor-binding domains, there are single amino-acid mutations that enable binding to new ACE2 orthologues. However, the effects of individual mutations can differ considerably between viruses, as shown by the N501Y mutation, which enhances the human ACE2-binding affinity of several SARS-CoV-2 variants of concern but substantially decreases it for SARS-CoV-1. Our results point to the deep ancestral origin and evolutionary plasticity of ACE2 binding, broadening the range of sarbecoviruses that should be considered to have spillover potential.",-1),d=[n,i];function l(c,h,b,u,p,v){return t(),s("div",null,d)}const m=a(o,[["render",l]]);export{g as __pageData,m as default}; diff --git a/assets/papers_2022_starr_a.md.DHkPF2CP.lean.js b/assets/papers_2022_starr_a.md.S2Zs3F-f.lean.js similarity index 97% rename from assets/papers_2022_starr_a.md.DHkPF2CP.lean.js rename to assets/papers_2022_starr_a.md.S2Zs3F-f.lean.js index f5f1b67..a99970c 100644 --- a/assets/papers_2022_starr_a.md.DHkPF2CP.lean.js +++ b/assets/papers_2022_starr_a.md.S2Zs3F-f.lean.js @@ -1 +1 @@ -import{_ as a,c as s,o as t,b as e,d as r}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"ACE2 binding is an ancestral and evolvable trait of sarbecoviruses","description":"","frontmatter":{"layout":"paper","title":"ACE2 binding is an ancestral and evolvable trait of sarbecoviruses","date":"2022-03-31","authors":["Tyler N Starr","Samantha K Zepeda","Alexandra C Walls","Allison J Greaney","Sergey Alkhovsky","David Veesler","Jesse D Bloom"],"journal":"Nature","doi":"10.1038/s41586-022-04464-z","link":"https://www.nature.com/articles/s41586-022-04464-z","image":"/assets/papers/2022_starr_a.jpg","keywords":["Coronavirus","Phylogenetics","Yeast display"]},"headers":[],"relativePath":"papers/2022_starr_a.md","filePath":"papers/2022_starr_a.md"}'),o={name:"papers/2022_starr_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"Two different sarbecoviruses have caused major human outbreaks in the past two decades. Both of these sarbecoviruses, SARS-CoV-1 and SARS-CoV-2, engage ACE2 through the spike receptor-binding domain. However, binding to ACE2 orthologues of humans, bats and other species has been observed only sporadically among the broader diversity of bat sarbecoviruses. Here we use high-throughput assays to trace the evolutionary history of ACE2 binding across a diverse range of sarbecoviruses and ACE2 orthologues. We find that ACE2 binding is an ancestral trait of sarbecovirus receptor-binding domains that has subsequently been lost in some clades. Furthermore, we reveal that bat sarbecoviruses from outside Asia can bind to ACE2. Moreover, ACE2 binding is highly evolvable—for many sarbecovirus receptor-binding domains, there are single amino-acid mutations that enable binding to new ACE2 orthologues. However, the effects of individual mutations can differ considerably between viruses, as shown by the N501Y mutation, which enhances the human ACE2-binding affinity of several SARS-CoV-2 variants of concern but substantially decreases it for SARS-CoV-1. Our results point to the deep ancestral origin and evolutionary plasticity of ACE2 binding, broadening the range of sarbecoviruses that should be considered to have spillover potential.",-1),d=[n,i];function l(c,h,b,u,p,v){return t(),s("div",null,d)}const m=a(o,[["render",l]]);export{g as __pageData,m as default}; +import{_ as a,c as s,o as t,b as e,d as r}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"ACE2 binding is an ancestral and evolvable trait of sarbecoviruses","description":"","frontmatter":{"layout":"paper","title":"ACE2 binding is an ancestral and evolvable trait of sarbecoviruses","date":"2022-03-31","authors":["Tyler N Starr","Samantha K Zepeda","Alexandra C Walls","Allison J Greaney","Sergey Alkhovsky","David Veesler","Jesse D Bloom"],"journal":"Nature","doi":"10.1038/s41586-022-04464-z","link":"https://www.nature.com/articles/s41586-022-04464-z","image":"/assets/papers/2022_starr_a.jpg","keywords":["Coronavirus","Phylogenetics","Yeast display"]},"headers":[],"relativePath":"papers/2022_starr_a.md","filePath":"papers/2022_starr_a.md"}'),o={name:"papers/2022_starr_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"Two different sarbecoviruses have caused major human outbreaks in the past two decades. Both of these sarbecoviruses, SARS-CoV-1 and SARS-CoV-2, engage ACE2 through the spike receptor-binding domain. However, binding to ACE2 orthologues of humans, bats and other species has been observed only sporadically among the broader diversity of bat sarbecoviruses. Here we use high-throughput assays to trace the evolutionary history of ACE2 binding across a diverse range of sarbecoviruses and ACE2 orthologues. We find that ACE2 binding is an ancestral trait of sarbecovirus receptor-binding domains that has subsequently been lost in some clades. Furthermore, we reveal that bat sarbecoviruses from outside Asia can bind to ACE2. Moreover, ACE2 binding is highly evolvable—for many sarbecovirus receptor-binding domains, there are single amino-acid mutations that enable binding to new ACE2 orthologues. However, the effects of individual mutations can differ considerably between viruses, as shown by the N501Y mutation, which enhances the human ACE2-binding affinity of several SARS-CoV-2 variants of concern but substantially decreases it for SARS-CoV-1. Our results point to the deep ancestral origin and evolutionary plasticity of ACE2 binding, broadening the range of sarbecoviruses that should be considered to have spillover potential.",-1),d=[n,i];function l(c,h,b,u,p,v){return t(),s("div",null,d)}const m=a(o,[["render",l]]);export{g as __pageData,m as default}; diff --git a/assets/papers_2022_starr_greaney_a.md.C9spTYQp.js b/assets/papers_2022_starr_greaney_a.md.D5j0_yFr.js similarity index 98% rename from assets/papers_2022_starr_greaney_a.md.C9spTYQp.js rename to assets/papers_2022_starr_greaney_a.md.D5j0_yFr.js index 0a04eb0..d8628e5 100644 --- a/assets/papers_2022_starr_greaney_a.md.C9spTYQp.js +++ b/assets/papers_2022_starr_greaney_a.md.D5j0_yFr.js @@ -1 +1 @@ -import{_ as a,c as n,o as t,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains","date":"2022-11-18","authors":["Tyler N Starr*","Allison J Greaney*","Cameron M Stewart","Alexandra C Walls","William W Hannon","David Veesler","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1010951","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010951","image":"/assets/papers/2022_starr_greaney_a.png","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2022_starr_greaney_a.md","filePath":"papers/2022_starr_greaney_a.md"}'),s={name:"papers/2022_starr_greaney_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"SARS-CoV-2 continues to acquire mutations in the spike receptor-binding domain (RBD) that impact ACE2 receptor binding, folding stability, and antibody recognition. Deep mutational scanning prospectively characterizes the impacts of mutations on these biochemical properties, enabling rapid assessment of new mutations seen during viral surveillance. However, the effects of mutations can change as the virus evolves, requiring updated deep mutational scans. We determined the impacts of all single amino acid mutations in the Omicron BA.1 and BA.2 RBDs on ACE2-binding affinity, RBD folding, and escape from binding by the LY-CoV1404 (bebtelovimab) monoclonal antibody. The effects of some mutations in Omicron RBDs differ from those measured in the ancestral Wuhan-Hu-1 background. These epistatic shifts largely resemble those previously seen in the Alpha variant due to the convergent epistatically modifying N501Y substitution. However, Omicron variants show additional lineage-specific shifts, including examples of the epistatic phenomenon of entrenchment that causes the Q498R and N501Y substitutions present in Omicron to be more favorable in that background than in earlier viral strains. In contrast, the Omicron substitution Q493R exhibits no sign of entrenchment, with the derived state, R493, being as unfavorable for ACE2 binding in Omicron RBDs as in Wuhan-Hu-1. Likely for this reason, the R493Q reversion has occurred in Omicron sub-variants including BA.4/BA.5 and BA.2.75, where the affinity buffer from R493Q reversion may potentiate concurrent antigenic change. Consistent with prior studies, we find that Omicron RBDs have reduced expression, and identify candidate stabilizing mutations that ameliorate this deficit. Last, our maps highlight a broadening of the sites of escape from LY-CoV1404 antibody binding in BA.1 and BA.2 compared to the ancestral Wuhan-Hu-1 background. These BA.1 and BA.2 deep mutational scanning datasets identify shifts in the RBD mutational landscape and inform ongoing efforts in viral surveillance.",-1),c=[o,r];function d(l,h,p,m,u,f){return t(),n("div",null,c)}const _=a(s,[["render",d]]);export{b as __pageData,_ as default}; +import{_ as a,c as n,o as t,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains","date":"2022-11-18","authors":["Tyler N Starr*","Allison J Greaney*","Cameron M Stewart","Alexandra C Walls","William W Hannon","David Veesler","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1010951","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010951","image":"/assets/papers/2022_starr_greaney_a.png","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2022_starr_greaney_a.md","filePath":"papers/2022_starr_greaney_a.md"}'),s={name:"papers/2022_starr_greaney_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"SARS-CoV-2 continues to acquire mutations in the spike receptor-binding domain (RBD) that impact ACE2 receptor binding, folding stability, and antibody recognition. Deep mutational scanning prospectively characterizes the impacts of mutations on these biochemical properties, enabling rapid assessment of new mutations seen during viral surveillance. However, the effects of mutations can change as the virus evolves, requiring updated deep mutational scans. We determined the impacts of all single amino acid mutations in the Omicron BA.1 and BA.2 RBDs on ACE2-binding affinity, RBD folding, and escape from binding by the LY-CoV1404 (bebtelovimab) monoclonal antibody. The effects of some mutations in Omicron RBDs differ from those measured in the ancestral Wuhan-Hu-1 background. These epistatic shifts largely resemble those previously seen in the Alpha variant due to the convergent epistatically modifying N501Y substitution. However, Omicron variants show additional lineage-specific shifts, including examples of the epistatic phenomenon of entrenchment that causes the Q498R and N501Y substitutions present in Omicron to be more favorable in that background than in earlier viral strains. In contrast, the Omicron substitution Q493R exhibits no sign of entrenchment, with the derived state, R493, being as unfavorable for ACE2 binding in Omicron RBDs as in Wuhan-Hu-1. Likely for this reason, the R493Q reversion has occurred in Omicron sub-variants including BA.4/BA.5 and BA.2.75, where the affinity buffer from R493Q reversion may potentiate concurrent antigenic change. Consistent with prior studies, we find that Omicron RBDs have reduced expression, and identify candidate stabilizing mutations that ameliorate this deficit. Last, our maps highlight a broadening of the sites of escape from LY-CoV1404 antibody binding in BA.1 and BA.2 compared to the ancestral Wuhan-Hu-1 background. These BA.1 and BA.2 deep mutational scanning datasets identify shifts in the RBD mutational landscape and inform ongoing efforts in viral surveillance.",-1),c=[o,r];function d(l,h,p,m,u,f){return t(),n("div",null,c)}const _=a(s,[["render",d]]);export{b as __pageData,_ as default}; diff --git a/assets/papers_2022_starr_greaney_a.md.C9spTYQp.lean.js b/assets/papers_2022_starr_greaney_a.md.D5j0_yFr.lean.js similarity index 98% rename from assets/papers_2022_starr_greaney_a.md.C9spTYQp.lean.js rename to assets/papers_2022_starr_greaney_a.md.D5j0_yFr.lean.js index 0a04eb0..d8628e5 100644 --- a/assets/papers_2022_starr_greaney_a.md.C9spTYQp.lean.js +++ b/assets/papers_2022_starr_greaney_a.md.D5j0_yFr.lean.js @@ -1 +1 @@ -import{_ as a,c as n,o as t,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains","date":"2022-11-18","authors":["Tyler N Starr*","Allison J Greaney*","Cameron M Stewart","Alexandra C Walls","William W Hannon","David Veesler","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1010951","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010951","image":"/assets/papers/2022_starr_greaney_a.png","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2022_starr_greaney_a.md","filePath":"papers/2022_starr_greaney_a.md"}'),s={name:"papers/2022_starr_greaney_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"SARS-CoV-2 continues to acquire mutations in the spike receptor-binding domain (RBD) that impact ACE2 receptor binding, folding stability, and antibody recognition. Deep mutational scanning prospectively characterizes the impacts of mutations on these biochemical properties, enabling rapid assessment of new mutations seen during viral surveillance. However, the effects of mutations can change as the virus evolves, requiring updated deep mutational scans. We determined the impacts of all single amino acid mutations in the Omicron BA.1 and BA.2 RBDs on ACE2-binding affinity, RBD folding, and escape from binding by the LY-CoV1404 (bebtelovimab) monoclonal antibody. The effects of some mutations in Omicron RBDs differ from those measured in the ancestral Wuhan-Hu-1 background. These epistatic shifts largely resemble those previously seen in the Alpha variant due to the convergent epistatically modifying N501Y substitution. However, Omicron variants show additional lineage-specific shifts, including examples of the epistatic phenomenon of entrenchment that causes the Q498R and N501Y substitutions present in Omicron to be more favorable in that background than in earlier viral strains. In contrast, the Omicron substitution Q493R exhibits no sign of entrenchment, with the derived state, R493, being as unfavorable for ACE2 binding in Omicron RBDs as in Wuhan-Hu-1. Likely for this reason, the R493Q reversion has occurred in Omicron sub-variants including BA.4/BA.5 and BA.2.75, where the affinity buffer from R493Q reversion may potentiate concurrent antigenic change. Consistent with prior studies, we find that Omicron RBDs have reduced expression, and identify candidate stabilizing mutations that ameliorate this deficit. Last, our maps highlight a broadening of the sites of escape from LY-CoV1404 antibody binding in BA.1 and BA.2 compared to the ancestral Wuhan-Hu-1 background. These BA.1 and BA.2 deep mutational scanning datasets identify shifts in the RBD mutational landscape and inform ongoing efforts in viral surveillance.",-1),c=[o,r];function d(l,h,p,m,u,f){return t(),n("div",null,c)}const _=a(s,[["render",d]]);export{b as __pageData,_ as default}; +import{_ as a,c as n,o as t,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains","date":"2022-11-18","authors":["Tyler N Starr*","Allison J Greaney*","Cameron M Stewart","Alexandra C Walls","William W Hannon","David Veesler","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1010951","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010951","image":"/assets/papers/2022_starr_greaney_a.png","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2022_starr_greaney_a.md","filePath":"papers/2022_starr_greaney_a.md"}'),s={name:"papers/2022_starr_greaney_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"SARS-CoV-2 continues to acquire mutations in the spike receptor-binding domain (RBD) that impact ACE2 receptor binding, folding stability, and antibody recognition. Deep mutational scanning prospectively characterizes the impacts of mutations on these biochemical properties, enabling rapid assessment of new mutations seen during viral surveillance. However, the effects of mutations can change as the virus evolves, requiring updated deep mutational scans. We determined the impacts of all single amino acid mutations in the Omicron BA.1 and BA.2 RBDs on ACE2-binding affinity, RBD folding, and escape from binding by the LY-CoV1404 (bebtelovimab) monoclonal antibody. The effects of some mutations in Omicron RBDs differ from those measured in the ancestral Wuhan-Hu-1 background. These epistatic shifts largely resemble those previously seen in the Alpha variant due to the convergent epistatically modifying N501Y substitution. However, Omicron variants show additional lineage-specific shifts, including examples of the epistatic phenomenon of entrenchment that causes the Q498R and N501Y substitutions present in Omicron to be more favorable in that background than in earlier viral strains. In contrast, the Omicron substitution Q493R exhibits no sign of entrenchment, with the derived state, R493, being as unfavorable for ACE2 binding in Omicron RBDs as in Wuhan-Hu-1. Likely for this reason, the R493Q reversion has occurred in Omicron sub-variants including BA.4/BA.5 and BA.2.75, where the affinity buffer from R493Q reversion may potentiate concurrent antigenic change. Consistent with prior studies, we find that Omicron RBDs have reduced expression, and identify candidate stabilizing mutations that ameliorate this deficit. Last, our maps highlight a broadening of the sites of escape from LY-CoV1404 antibody binding in BA.1 and BA.2 compared to the ancestral Wuhan-Hu-1 background. These BA.1 and BA.2 deep mutational scanning datasets identify shifts in the RBD mutational landscape and inform ongoing efforts in viral surveillance.",-1),c=[o,r];function d(l,h,p,m,u,f){return t(),n("div",null,c)}const _=a(s,[["render",d]]);export{b as __pageData,_ as default}; diff --git a/assets/papers_2022_starr_greaney_b.md.D1tEaQww.js b/assets/papers_2022_starr_greaney_b.md.DNdvVrrg.js similarity index 97% rename from assets/papers_2022_starr_greaney_b.md.D1tEaQww.js rename to assets/papers_2022_starr_greaney_b.md.DNdvVrrg.js index 2e3574f..e33492b 100644 --- a/assets/papers_2022_starr_greaney_b.md.D1tEaQww.js +++ b/assets/papers_2022_starr_greaney_b.md.DNdvVrrg.js @@ -1 +1 @@ -import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution","description":"","frontmatter":{"layout":"paper","title":"Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution","date":"2022-07-22","authors":["Tyler N Starr*","Allison J Greaney*","William W Hannon","Andrea N Loes","Kevin Hauser","Josh R Dillen","Elena Ferri","Ariana Ghez Farrell","Bernadeta Dadonaite","Matthew McCallum","Kenneth A Matreyek","Davide Corti","David Veesler","Gyorgy Snell","Jesse D Bloom"],"journal":"Science","doi":"10.1126/science.abo7896","link":"https://www.science.org/doi/full/10.1126/science.abo7896","image":"/assets/papers/2022_starr_greaney_b.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning","Epistasis"]},"headers":[],"relativePath":"papers/2022_starr_greaney_b.md","filePath":"papers/2022_starr_greaney_b.md"}'),s={name:"papers/2022_starr_greaney_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved variants with substitutions in the spike receptor-binding domain (RBD) that affect its affinity for angiotensin-converting enzyme 2 (ACE2) receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites—a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single–amino acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently Asn501→Tyr (N501Y), cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change—for example, enabling many of the antibody-escape substitutions in the Omicron RBD. These epistatic shifts occur despite high conservation of the overall RBD structure. Our data shed light on RBD sequence-function relationships and facilitate interpretation of ongoing SARS-CoV-2 evolution.",-1),l=[o,r];function c(d,h,u,p,f,m){return i(),a("div",null,l)}const b=t(s,[["render",c]]);export{g as __pageData,b as default}; +import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution","description":"","frontmatter":{"layout":"paper","title":"Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution","date":"2022-07-22","authors":["Tyler N Starr*","Allison J Greaney*","William W Hannon","Andrea N Loes","Kevin Hauser","Josh R Dillen","Elena Ferri","Ariana Ghez Farrell","Bernadeta Dadonaite","Matthew McCallum","Kenneth A Matreyek","Davide Corti","David Veesler","Gyorgy Snell","Jesse D Bloom"],"journal":"Science","doi":"10.1126/science.abo7896","link":"https://www.science.org/doi/full/10.1126/science.abo7896","image":"/assets/papers/2022_starr_greaney_b.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning","Epistasis"]},"headers":[],"relativePath":"papers/2022_starr_greaney_b.md","filePath":"papers/2022_starr_greaney_b.md"}'),s={name:"papers/2022_starr_greaney_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved variants with substitutions in the spike receptor-binding domain (RBD) that affect its affinity for angiotensin-converting enzyme 2 (ACE2) receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites—a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single–amino acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently Asn501→Tyr (N501Y), cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change—for example, enabling many of the antibody-escape substitutions in the Omicron RBD. These epistatic shifts occur despite high conservation of the overall RBD structure. Our data shed light on RBD sequence-function relationships and facilitate interpretation of ongoing SARS-CoV-2 evolution.",-1),l=[o,r];function c(d,h,u,p,f,m){return i(),a("div",null,l)}const b=t(s,[["render",c]]);export{g as __pageData,b as default}; diff --git a/assets/papers_2022_starr_greaney_b.md.D1tEaQww.lean.js b/assets/papers_2022_starr_greaney_b.md.DNdvVrrg.lean.js similarity index 97% rename from assets/papers_2022_starr_greaney_b.md.D1tEaQww.lean.js rename to assets/papers_2022_starr_greaney_b.md.DNdvVrrg.lean.js index 2e3574f..e33492b 100644 --- a/assets/papers_2022_starr_greaney_b.md.D1tEaQww.lean.js +++ b/assets/papers_2022_starr_greaney_b.md.DNdvVrrg.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution","description":"","frontmatter":{"layout":"paper","title":"Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution","date":"2022-07-22","authors":["Tyler N Starr*","Allison J Greaney*","William W Hannon","Andrea N Loes","Kevin Hauser","Josh R Dillen","Elena Ferri","Ariana Ghez Farrell","Bernadeta Dadonaite","Matthew McCallum","Kenneth A Matreyek","Davide Corti","David Veesler","Gyorgy Snell","Jesse D Bloom"],"journal":"Science","doi":"10.1126/science.abo7896","link":"https://www.science.org/doi/full/10.1126/science.abo7896","image":"/assets/papers/2022_starr_greaney_b.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning","Epistasis"]},"headers":[],"relativePath":"papers/2022_starr_greaney_b.md","filePath":"papers/2022_starr_greaney_b.md"}'),s={name:"papers/2022_starr_greaney_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved variants with substitutions in the spike receptor-binding domain (RBD) that affect its affinity for angiotensin-converting enzyme 2 (ACE2) receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites—a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single–amino acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently Asn501→Tyr (N501Y), cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change—for example, enabling many of the antibody-escape substitutions in the Omicron RBD. These epistatic shifts occur despite high conservation of the overall RBD structure. Our data shed light on RBD sequence-function relationships and facilitate interpretation of ongoing SARS-CoV-2 evolution.",-1),l=[o,r];function c(d,h,u,p,f,m){return i(),a("div",null,l)}const b=t(s,[["render",c]]);export{g as __pageData,b as default}; +import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution","description":"","frontmatter":{"layout":"paper","title":"Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution","date":"2022-07-22","authors":["Tyler N Starr*","Allison J Greaney*","William W Hannon","Andrea N Loes","Kevin Hauser","Josh R Dillen","Elena Ferri","Ariana Ghez Farrell","Bernadeta Dadonaite","Matthew McCallum","Kenneth A Matreyek","Davide Corti","David Veesler","Gyorgy Snell","Jesse D Bloom"],"journal":"Science","doi":"10.1126/science.abo7896","link":"https://www.science.org/doi/full/10.1126/science.abo7896","image":"/assets/papers/2022_starr_greaney_b.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning","Epistasis"]},"headers":[],"relativePath":"papers/2022_starr_greaney_b.md","filePath":"papers/2022_starr_greaney_b.md"}'),s={name:"papers/2022_starr_greaney_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved variants with substitutions in the spike receptor-binding domain (RBD) that affect its affinity for angiotensin-converting enzyme 2 (ACE2) receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites—a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single–amino acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently Asn501→Tyr (N501Y), cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change—for example, enabling many of the antibody-escape substitutions in the Omicron RBD. These epistatic shifts occur despite high conservation of the overall RBD structure. Our data shed light on RBD sequence-function relationships and facilitate interpretation of ongoing SARS-CoV-2 evolution.",-1),l=[o,r];function c(d,h,u,p,f,m){return i(),a("div",null,l)}const b=t(s,[["render",c]]);export{g as __pageData,b as default}; diff --git a/assets/papers_2022_yu.md.C3T-t2G0.js b/assets/papers_2022_yu.md.kTo3Hr8f.js similarity index 96% rename from assets/papers_2022_yu.md.C3T-t2G0.js rename to assets/papers_2022_yu.md.kTo3Hr8f.js index a66ff3b..d438a8a 100644 --- a/assets/papers_2022_yu.md.C3T-t2G0.js +++ b/assets/papers_2022_yu.md.kTo3Hr8f.js @@ -1 +1 @@ -import{_ as t,c as o,o as i,b as e,d as a}from"./chunks/framework.BqSDeblO.js";const f=JSON.parse('{"title":"A biophysical model of viral escape from polyclonal antibodies","description":"","frontmatter":{"layout":"paper","title":"A biophysical model of viral escape from polyclonal antibodies","date":"2022-07-01","authors":["Timothy C Yu","Zorian T Thornton","William W Hannon","William S DeWitt","Caelan E Radford","Frederick A Matsen IV","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac110","link":"https://academic.oup.com/ve/article/8/2/veac110/6889254","image":"/assets/papers/2022_yu.jpg","keywords":["Software tools","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2022_yu.md","filePath":"papers/2022_yu.md"}'),n={name:"papers/2022_yu.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),l=e("p",null,[a("A challenge in studying viral immune escape is determining how mutations combine to escape polyclonal antibodies, which can potentially target multiple distinct viral epitopes. Here we introduce a biophysical model of this process that partitions the total polyclonal antibody activity by epitope and then quantifies how each viral mutation affects the antibody activity against each epitope. We develop software that can use deep mutational scanning data to infer these properties for polyclonal antibody mixtures. We validate this software using a computationally simulated deep mutational scanning experiment and demonstrate that it enables the prediction of escape by arbitrary combinations of mutations. The software described in this paper is available at "),e("a",{href:"https://jbloomlab.github.io/polyclonal",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/polyclonal"),a(".")],-1),r=[s,l];function c(p,d,h,m,u,b){return i(),o("div",null,r)}const _=t(n,[["render",c]]);export{f as __pageData,_ as default}; +import{_ as t,c as o,o as i,b as e,d as a}from"./chunks/framework.D4bY2S_W.js";const f=JSON.parse('{"title":"A biophysical model of viral escape from polyclonal antibodies","description":"","frontmatter":{"layout":"paper","title":"A biophysical model of viral escape from polyclonal antibodies","date":"2022-07-01","authors":["Timothy C Yu","Zorian T Thornton","William W Hannon","William S DeWitt","Caelan E Radford","Frederick A Matsen IV","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac110","link":"https://academic.oup.com/ve/article/8/2/veac110/6889254","image":"/assets/papers/2022_yu.jpg","keywords":["Software tools","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2022_yu.md","filePath":"papers/2022_yu.md"}'),n={name:"papers/2022_yu.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),l=e("p",null,[a("A challenge in studying viral immune escape is determining how mutations combine to escape polyclonal antibodies, which can potentially target multiple distinct viral epitopes. Here we introduce a biophysical model of this process that partitions the total polyclonal antibody activity by epitope and then quantifies how each viral mutation affects the antibody activity against each epitope. We develop software that can use deep mutational scanning data to infer these properties for polyclonal antibody mixtures. We validate this software using a computationally simulated deep mutational scanning experiment and demonstrate that it enables the prediction of escape by arbitrary combinations of mutations. The software described in this paper is available at "),e("a",{href:"https://jbloomlab.github.io/polyclonal",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/polyclonal"),a(".")],-1),r=[s,l];function c(p,d,h,m,u,b){return i(),o("div",null,r)}const _=t(n,[["render",c]]);export{f as __pageData,_ as default}; diff --git a/assets/papers_2022_yu.md.C3T-t2G0.lean.js b/assets/papers_2022_yu.md.kTo3Hr8f.lean.js similarity index 96% rename from assets/papers_2022_yu.md.C3T-t2G0.lean.js rename to assets/papers_2022_yu.md.kTo3Hr8f.lean.js index a66ff3b..d438a8a 100644 --- a/assets/papers_2022_yu.md.C3T-t2G0.lean.js +++ b/assets/papers_2022_yu.md.kTo3Hr8f.lean.js @@ -1 +1 @@ -import{_ as t,c as o,o as i,b as e,d as a}from"./chunks/framework.BqSDeblO.js";const f=JSON.parse('{"title":"A biophysical model of viral escape from polyclonal antibodies","description":"","frontmatter":{"layout":"paper","title":"A biophysical model of viral escape from polyclonal antibodies","date":"2022-07-01","authors":["Timothy C Yu","Zorian T Thornton","William W Hannon","William S DeWitt","Caelan E Radford","Frederick A Matsen IV","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac110","link":"https://academic.oup.com/ve/article/8/2/veac110/6889254","image":"/assets/papers/2022_yu.jpg","keywords":["Software tools","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2022_yu.md","filePath":"papers/2022_yu.md"}'),n={name:"papers/2022_yu.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),l=e("p",null,[a("A challenge in studying viral immune escape is determining how mutations combine to escape polyclonal antibodies, which can potentially target multiple distinct viral epitopes. Here we introduce a biophysical model of this process that partitions the total polyclonal antibody activity by epitope and then quantifies how each viral mutation affects the antibody activity against each epitope. We develop software that can use deep mutational scanning data to infer these properties for polyclonal antibody mixtures. We validate this software using a computationally simulated deep mutational scanning experiment and demonstrate that it enables the prediction of escape by arbitrary combinations of mutations. The software described in this paper is available at "),e("a",{href:"https://jbloomlab.github.io/polyclonal",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/polyclonal"),a(".")],-1),r=[s,l];function c(p,d,h,m,u,b){return i(),o("div",null,r)}const _=t(n,[["render",c]]);export{f as __pageData,_ as default}; +import{_ as t,c as o,o as i,b as e,d as a}from"./chunks/framework.D4bY2S_W.js";const f=JSON.parse('{"title":"A biophysical model of viral escape from polyclonal antibodies","description":"","frontmatter":{"layout":"paper","title":"A biophysical model of viral escape from polyclonal antibodies","date":"2022-07-01","authors":["Timothy C Yu","Zorian T Thornton","William W Hannon","William S DeWitt","Caelan E Radford","Frederick A Matsen IV","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac110","link":"https://academic.oup.com/ve/article/8/2/veac110/6889254","image":"/assets/papers/2022_yu.jpg","keywords":["Software tools","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2022_yu.md","filePath":"papers/2022_yu.md"}'),n={name:"papers/2022_yu.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),l=e("p",null,[a("A challenge in studying viral immune escape is determining how mutations combine to escape polyclonal antibodies, which can potentially target multiple distinct viral epitopes. Here we introduce a biophysical model of this process that partitions the total polyclonal antibody activity by epitope and then quantifies how each viral mutation affects the antibody activity against each epitope. We develop software that can use deep mutational scanning data to infer these properties for polyclonal antibody mixtures. We validate this software using a computationally simulated deep mutational scanning experiment and demonstrate that it enables the prediction of escape by arbitrary combinations of mutations. The software described in this paper is available at "),e("a",{href:"https://jbloomlab.github.io/polyclonal",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/polyclonal"),a(".")],-1),r=[s,l];function c(p,d,h,m,u,b){return i(),o("div",null,r)}const _=t(n,[["render",c]]);export{f as __pageData,_ as default}; diff --git a/assets/papers_2023_bacsik.md.D763YfIs.js b/assets/papers_2023_bacsik.md.CSLMWJ8m.js similarity index 97% rename from assets/papers_2023_bacsik.md.D763YfIs.js rename to assets/papers_2023_bacsik.md.CSLMWJ8m.js index 97f6fd7..83afa9f 100644 --- a/assets/papers_2023_bacsik.md.D763YfIs.js +++ b/assets/papers_2023_bacsik.md.CSLMWJ8m.js @@ -1 +1 @@ -import{_ as t,c as n,o as r,b as e,d as a}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Influenza virus transcription and progeny production are poorly correlated in single cells","description":"","frontmatter":{"layout":"paper","title":"Influenza virus transcription and progeny production are poorly correlated in single cells","date":"2023-09-07","authors":["David J Bacsik","Bernadeta Dadonaite","Andrew Butler","Allison J Greaney","Nicholas S Heaton","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.86852.2","link":"https://elifesciences.org/articles/86852","image":"/assets/papers/2023_bacsik.jpg","selected":true,"keywords":["Single-cell sequencing","Influenza"]},"headers":[],"relativePath":"papers/2023_bacsik.md","filePath":"papers/2023_bacsik.md"}'),o={name:"papers/2023_bacsik.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The ultimate success of a viral infection at the cellular level is determined by the number of progeny virions produced. However, most single-cell studies of infection quantify the expression of viral transcripts and proteins, rather than the amount of progeny virions released from infected cells. Here, we overcome this limitation by simultaneously measuring transcription and progeny production from single influenza virus-infected cells by embedding nucleotide barcodes in the viral genome. We find that viral transcription and progeny production are poorly correlated in single cells. The cells that transcribe the most viral mRNA do not produce the most viral progeny and often represent aberrant infections that fail to express the influenza NS gene. However, only some of the discrepancy between transcription and progeny production can be explained by viral gene absence or mutations: there is also a wide range of progeny production among cells infected by complete unmutated virions. Overall, our results show that viral transcription is a relatively poor predictor of an infected cell’s contribution to the progeny population.",-1),l=[i,s];function c(d,p,u,f,h,m){return r(),n("div",null,l)}const y=t(o,[["render",c]]);export{b as __pageData,y as default}; +import{_ as t,c as n,o as r,b as e,d as a}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Influenza virus transcription and progeny production are poorly correlated in single cells","description":"","frontmatter":{"layout":"paper","title":"Influenza virus transcription and progeny production are poorly correlated in single cells","date":"2023-09-07","authors":["David J Bacsik","Bernadeta Dadonaite","Andrew Butler","Allison J Greaney","Nicholas S Heaton","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.86852.2","link":"https://elifesciences.org/articles/86852","image":"/assets/papers/2023_bacsik.jpg","selected":true,"keywords":["Single-cell sequencing","Influenza"]},"headers":[],"relativePath":"papers/2023_bacsik.md","filePath":"papers/2023_bacsik.md"}'),o={name:"papers/2023_bacsik.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The ultimate success of a viral infection at the cellular level is determined by the number of progeny virions produced. However, most single-cell studies of infection quantify the expression of viral transcripts and proteins, rather than the amount of progeny virions released from infected cells. Here, we overcome this limitation by simultaneously measuring transcription and progeny production from single influenza virus-infected cells by embedding nucleotide barcodes in the viral genome. We find that viral transcription and progeny production are poorly correlated in single cells. The cells that transcribe the most viral mRNA do not produce the most viral progeny and often represent aberrant infections that fail to express the influenza NS gene. However, only some of the discrepancy between transcription and progeny production can be explained by viral gene absence or mutations: there is also a wide range of progeny production among cells infected by complete unmutated virions. Overall, our results show that viral transcription is a relatively poor predictor of an infected cell’s contribution to the progeny population.",-1),l=[i,s];function c(d,p,u,f,h,m){return r(),n("div",null,l)}const y=t(o,[["render",c]]);export{b as __pageData,y as default}; diff --git a/assets/papers_2023_bacsik.md.D763YfIs.lean.js b/assets/papers_2023_bacsik.md.CSLMWJ8m.lean.js similarity index 97% rename from assets/papers_2023_bacsik.md.D763YfIs.lean.js rename to assets/papers_2023_bacsik.md.CSLMWJ8m.lean.js index 97f6fd7..83afa9f 100644 --- a/assets/papers_2023_bacsik.md.D763YfIs.lean.js +++ b/assets/papers_2023_bacsik.md.CSLMWJ8m.lean.js @@ -1 +1 @@ -import{_ as t,c as n,o as r,b as e,d as a}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Influenza virus transcription and progeny production are poorly correlated in single cells","description":"","frontmatter":{"layout":"paper","title":"Influenza virus transcription and progeny production are poorly correlated in single cells","date":"2023-09-07","authors":["David J Bacsik","Bernadeta Dadonaite","Andrew Butler","Allison J Greaney","Nicholas S Heaton","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.86852.2","link":"https://elifesciences.org/articles/86852","image":"/assets/papers/2023_bacsik.jpg","selected":true,"keywords":["Single-cell sequencing","Influenza"]},"headers":[],"relativePath":"papers/2023_bacsik.md","filePath":"papers/2023_bacsik.md"}'),o={name:"papers/2023_bacsik.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The ultimate success of a viral infection at the cellular level is determined by the number of progeny virions produced. However, most single-cell studies of infection quantify the expression of viral transcripts and proteins, rather than the amount of progeny virions released from infected cells. Here, we overcome this limitation by simultaneously measuring transcription and progeny production from single influenza virus-infected cells by embedding nucleotide barcodes in the viral genome. We find that viral transcription and progeny production are poorly correlated in single cells. The cells that transcribe the most viral mRNA do not produce the most viral progeny and often represent aberrant infections that fail to express the influenza NS gene. However, only some of the discrepancy between transcription and progeny production can be explained by viral gene absence or mutations: there is also a wide range of progeny production among cells infected by complete unmutated virions. Overall, our results show that viral transcription is a relatively poor predictor of an infected cell’s contribution to the progeny population.",-1),l=[i,s];function c(d,p,u,f,h,m){return r(),n("div",null,l)}const y=t(o,[["render",c]]);export{b as __pageData,y as default}; +import{_ as t,c as n,o as r,b as e,d as a}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Influenza virus transcription and progeny production are poorly correlated in single cells","description":"","frontmatter":{"layout":"paper","title":"Influenza virus transcription and progeny production are poorly correlated in single cells","date":"2023-09-07","authors":["David J Bacsik","Bernadeta Dadonaite","Andrew Butler","Allison J Greaney","Nicholas S Heaton","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.86852.2","link":"https://elifesciences.org/articles/86852","image":"/assets/papers/2023_bacsik.jpg","selected":true,"keywords":["Single-cell sequencing","Influenza"]},"headers":[],"relativePath":"papers/2023_bacsik.md","filePath":"papers/2023_bacsik.md"}'),o={name:"papers/2023_bacsik.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The ultimate success of a viral infection at the cellular level is determined by the number of progeny virions produced. However, most single-cell studies of infection quantify the expression of viral transcripts and proteins, rather than the amount of progeny virions released from infected cells. Here, we overcome this limitation by simultaneously measuring transcription and progeny production from single influenza virus-infected cells by embedding nucleotide barcodes in the viral genome. We find that viral transcription and progeny production are poorly correlated in single cells. The cells that transcribe the most viral mRNA do not produce the most viral progeny and often represent aberrant infections that fail to express the influenza NS gene. However, only some of the discrepancy between transcription and progeny production can be explained by viral gene absence or mutations: there is also a wide range of progeny production among cells infected by complete unmutated virions. Overall, our results show that viral transcription is a relatively poor predictor of an infected cell’s contribution to the progeny population.",-1),l=[i,s];function c(d,p,u,f,h,m){return r(),n("div",null,l)}const y=t(o,[["render",c]]);export{b as __pageData,y as default}; diff --git a/assets/papers_2023_bloom_a.md.CzB-HA3V.js b/assets/papers_2023_bloom_a.md.BCf1Dh2c.js similarity index 95% rename from assets/papers_2023_bloom_a.md.CzB-HA3V.js rename to assets/papers_2023_bloom_a.md.BCf1Dh2c.js index 8db8fae..c413303 100644 --- a/assets/papers_2023_bloom_a.md.CzB-HA3V.js +++ b/assets/papers_2023_bloom_a.md.BCf1Dh2c.js @@ -1 +1 @@ -import{_ as a,c as t,o,b as e,d as s}from"./chunks/framework.BqSDeblO.js";const S=JSON.parse('{"title":"Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market","description":"","frontmatter":{"layout":"paper","title":"Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market","date":"2023-07-01","authors":["Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/vead050","link":"https://academic.oup.com/ve/article/9/2/vead050/7249794","image":"/assets/papers/2023_bloom_a.jpg","keywords":["SARS-CoV-2"]},"headers":[],"relativePath":"papers/2023_bloom_a.md","filePath":"papers/2023_bloom_a.md"}'),n={name:"papers/2023_bloom_a.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"The role of the Huanan Seafood Market in the early severe acute respiratory syndrome virus 2 (SARS-CoV-2) outbreak remains unclear. Recently, the Chinese Centers for Disease Control (CDC) released data from deep sequencing of environmental samples collected from the market after it was closed on 1 January 2020. Prior to this release, Crits-Christoph et al. analyzed data from a subset of the samples. Both that study and the Chinese CDC study concurred that the samples contained genetic material from a variety of species, including some like raccoon dogs that are susceptible to SARS-CoV-2. However, neither study systematically analyzed the relationship between the amount of genetic material from SARS-CoV-2 and different animal species. Here I implement a fully reproducible computational pipeline that jointly analyzes the number of reads mapping to SARS-CoV-2 and the mitochondrial genomes of chordate species across the full set of samples. I validate the presence of genetic material from numerous species and calculate mammalian mitochondrial compositions similar to those reported by Crits-Christoph et al. However, the SARS-CoV-2 content of the environmental samples is generally very low: only 21 of 176 samples contain more than ten SARS-CoV-2 reads, despite most samples being sequenced to depths exceeding 10**8 total reads. None of the samples with double-digit numbers of SARS-CoV-2 reads have a substantial fraction of their mitochondrial material from any non-human susceptible species. Only one of the fourteen samples with at least a fifth of the chordate mitochondrial material from raccoon dogs contains any SARS-CoV-2 reads, and that sample only has 1 of ~200,000,000 reads mapping to SARS-CoV-2. Instead, SARS-CoV-2 reads are most correlated with reads mapping to various fish, such as catfish and largemouth bass. These results suggest that while metagenomic analysis of the environmental samples is useful for identifying animals or animal products sold at the market, co-mingling of animal and viral genetic material is unlikely to reliably indicate whether any animals were infected by SARS-CoV-2.",-1),l=[r,i];function m(c,d,h,p,f,u){return o(),t("div",null,l)}const b=a(n,[["render",m]]);export{S as __pageData,b as default}; +import{_ as a,c as t,o,b as e,d as s}from"./chunks/framework.D4bY2S_W.js";const S=JSON.parse('{"title":"Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market","description":"","frontmatter":{"layout":"paper","title":"Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market","date":"2023-07-01","authors":["Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/vead050","link":"https://academic.oup.com/ve/article/9/2/vead050/7249794","image":"/assets/papers/2023_bloom_a.jpg","keywords":["SARS-CoV-2"]},"headers":[],"relativePath":"papers/2023_bloom_a.md","filePath":"papers/2023_bloom_a.md"}'),n={name:"papers/2023_bloom_a.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"The role of the Huanan Seafood Market in the early severe acute respiratory syndrome virus 2 (SARS-CoV-2) outbreak remains unclear. Recently, the Chinese Centers for Disease Control (CDC) released data from deep sequencing of environmental samples collected from the market after it was closed on 1 January 2020. Prior to this release, Crits-Christoph et al. analyzed data from a subset of the samples. Both that study and the Chinese CDC study concurred that the samples contained genetic material from a variety of species, including some like raccoon dogs that are susceptible to SARS-CoV-2. However, neither study systematically analyzed the relationship between the amount of genetic material from SARS-CoV-2 and different animal species. Here I implement a fully reproducible computational pipeline that jointly analyzes the number of reads mapping to SARS-CoV-2 and the mitochondrial genomes of chordate species across the full set of samples. I validate the presence of genetic material from numerous species and calculate mammalian mitochondrial compositions similar to those reported by Crits-Christoph et al. However, the SARS-CoV-2 content of the environmental samples is generally very low: only 21 of 176 samples contain more than ten SARS-CoV-2 reads, despite most samples being sequenced to depths exceeding 10**8 total reads. None of the samples with double-digit numbers of SARS-CoV-2 reads have a substantial fraction of their mitochondrial material from any non-human susceptible species. Only one of the fourteen samples with at least a fifth of the chordate mitochondrial material from raccoon dogs contains any SARS-CoV-2 reads, and that sample only has 1 of ~200,000,000 reads mapping to SARS-CoV-2. Instead, SARS-CoV-2 reads are most correlated with reads mapping to various fish, such as catfish and largemouth bass. These results suggest that while metagenomic analysis of the environmental samples is useful for identifying animals or animal products sold at the market, co-mingling of animal and viral genetic material is unlikely to reliably indicate whether any animals were infected by SARS-CoV-2.",-1),l=[r,i];function m(c,d,h,p,f,u){return o(),t("div",null,l)}const b=a(n,[["render",m]]);export{S as __pageData,b as default}; diff --git a/assets/papers_2023_bloom_a.md.CzB-HA3V.lean.js b/assets/papers_2023_bloom_a.md.BCf1Dh2c.lean.js similarity index 95% rename from assets/papers_2023_bloom_a.md.CzB-HA3V.lean.js rename to assets/papers_2023_bloom_a.md.BCf1Dh2c.lean.js index 8db8fae..c413303 100644 --- a/assets/papers_2023_bloom_a.md.CzB-HA3V.lean.js +++ b/assets/papers_2023_bloom_a.md.BCf1Dh2c.lean.js @@ -1 +1 @@ -import{_ as a,c as t,o,b as e,d as s}from"./chunks/framework.BqSDeblO.js";const S=JSON.parse('{"title":"Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market","description":"","frontmatter":{"layout":"paper","title":"Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market","date":"2023-07-01","authors":["Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/vead050","link":"https://academic.oup.com/ve/article/9/2/vead050/7249794","image":"/assets/papers/2023_bloom_a.jpg","keywords":["SARS-CoV-2"]},"headers":[],"relativePath":"papers/2023_bloom_a.md","filePath":"papers/2023_bloom_a.md"}'),n={name:"papers/2023_bloom_a.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"The role of the Huanan Seafood Market in the early severe acute respiratory syndrome virus 2 (SARS-CoV-2) outbreak remains unclear. Recently, the Chinese Centers for Disease Control (CDC) released data from deep sequencing of environmental samples collected from the market after it was closed on 1 January 2020. Prior to this release, Crits-Christoph et al. analyzed data from a subset of the samples. Both that study and the Chinese CDC study concurred that the samples contained genetic material from a variety of species, including some like raccoon dogs that are susceptible to SARS-CoV-2. However, neither study systematically analyzed the relationship between the amount of genetic material from SARS-CoV-2 and different animal species. Here I implement a fully reproducible computational pipeline that jointly analyzes the number of reads mapping to SARS-CoV-2 and the mitochondrial genomes of chordate species across the full set of samples. I validate the presence of genetic material from numerous species and calculate mammalian mitochondrial compositions similar to those reported by Crits-Christoph et al. However, the SARS-CoV-2 content of the environmental samples is generally very low: only 21 of 176 samples contain more than ten SARS-CoV-2 reads, despite most samples being sequenced to depths exceeding 10**8 total reads. None of the samples with double-digit numbers of SARS-CoV-2 reads have a substantial fraction of their mitochondrial material from any non-human susceptible species. Only one of the fourteen samples with at least a fifth of the chordate mitochondrial material from raccoon dogs contains any SARS-CoV-2 reads, and that sample only has 1 of ~200,000,000 reads mapping to SARS-CoV-2. Instead, SARS-CoV-2 reads are most correlated with reads mapping to various fish, such as catfish and largemouth bass. These results suggest that while metagenomic analysis of the environmental samples is useful for identifying animals or animal products sold at the market, co-mingling of animal and viral genetic material is unlikely to reliably indicate whether any animals were infected by SARS-CoV-2.",-1),l=[r,i];function m(c,d,h,p,f,u){return o(),t("div",null,l)}const b=a(n,[["render",m]]);export{S as __pageData,b as default}; +import{_ as a,c as t,o,b as e,d as s}from"./chunks/framework.D4bY2S_W.js";const S=JSON.parse('{"title":"Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market","description":"","frontmatter":{"layout":"paper","title":"Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market","date":"2023-07-01","authors":["Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/vead050","link":"https://academic.oup.com/ve/article/9/2/vead050/7249794","image":"/assets/papers/2023_bloom_a.jpg","keywords":["SARS-CoV-2"]},"headers":[],"relativePath":"papers/2023_bloom_a.md","filePath":"papers/2023_bloom_a.md"}'),n={name:"papers/2023_bloom_a.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"The role of the Huanan Seafood Market in the early severe acute respiratory syndrome virus 2 (SARS-CoV-2) outbreak remains unclear. Recently, the Chinese Centers for Disease Control (CDC) released data from deep sequencing of environmental samples collected from the market after it was closed on 1 January 2020. Prior to this release, Crits-Christoph et al. analyzed data from a subset of the samples. Both that study and the Chinese CDC study concurred that the samples contained genetic material from a variety of species, including some like raccoon dogs that are susceptible to SARS-CoV-2. However, neither study systematically analyzed the relationship between the amount of genetic material from SARS-CoV-2 and different animal species. Here I implement a fully reproducible computational pipeline that jointly analyzes the number of reads mapping to SARS-CoV-2 and the mitochondrial genomes of chordate species across the full set of samples. I validate the presence of genetic material from numerous species and calculate mammalian mitochondrial compositions similar to those reported by Crits-Christoph et al. However, the SARS-CoV-2 content of the environmental samples is generally very low: only 21 of 176 samples contain more than ten SARS-CoV-2 reads, despite most samples being sequenced to depths exceeding 10**8 total reads. None of the samples with double-digit numbers of SARS-CoV-2 reads have a substantial fraction of their mitochondrial material from any non-human susceptible species. Only one of the fourteen samples with at least a fifth of the chordate mitochondrial material from raccoon dogs contains any SARS-CoV-2 reads, and that sample only has 1 of ~200,000,000 reads mapping to SARS-CoV-2. Instead, SARS-CoV-2 reads are most correlated with reads mapping to various fish, such as catfish and largemouth bass. These results suggest that while metagenomic analysis of the environmental samples is useful for identifying animals or animal products sold at the market, co-mingling of animal and viral genetic material is unlikely to reliably indicate whether any animals were infected by SARS-CoV-2.",-1),l=[r,i];function m(c,d,h,p,f,u){return o(),t("div",null,l)}const b=a(n,[["render",m]]);export{S as __pageData,b as default}; diff --git a/assets/papers_2023_bloom_b.md.CKQthdh3.js b/assets/papers_2023_bloom_b.md.DAvFQSAm.js similarity index 94% rename from assets/papers_2023_bloom_b.md.CKQthdh3.js rename to assets/papers_2023_bloom_b.md.DAvFQSAm.js index 30a707a..ab32f2d 100644 --- a/assets/papers_2023_bloom_b.md.CKQthdh3.js +++ b/assets/papers_2023_bloom_b.md.DAvFQSAm.js @@ -1 +1 @@ -import{_ as t,c as a,o,b as e,d as s}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Evolution of the SARS-CoV-2 mutational spectrum","description":"","frontmatter":{"layout":"paper","title":"Evolution of the SARS-CoV-2 mutational spectrum","date":"2023-04-11","authors":["Jesse D Bloom","Annabel C Beichman","Richard A Neher","Kelley Harris"],"journal":"Molecular Biology and Evolution","doi":"10.1093/molbev/msad085","link":"https://academic.oup.com/mbe/article/40/4/msad085/7113660","image":"/assets/papers/2023_bloom_b.jpg","keywords":["SARS-CoV-2","Phylogenetics"]},"headers":[],"relativePath":"papers/2023_bloom_b.md","filePath":"papers/2023_bloom_b.md"}'),i={name:"papers/2023_bloom_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"SARS-CoV-2 evolves rapidly in part because of its high mutation rate. Here, we examine whether this mutational process itself has changed during viral evolution. To do this, we quantify the relative rates of different types of single-nucleotide mutations at 4-fold degenerate sites in the viral genome across millions of human SARS-CoV-2 sequences. We find clear shifts in the relative rates of several types of mutations during SARS-CoV-2 evolution. The most striking trend is a roughly 2-fold decrease in the relative rate of G→T mutations in Omicron versus early clades, as was recently noted by Ruis et al. (2022. Mutational spectra distinguish SARS-CoV-2 replication niches. bioRxiv, doi:10.1101/2022.09.27.509649). There is also a decrease in the relative rate of C→T mutations in Delta, and other subtle changes in the mutation spectrum along the phylogeny. We speculate that these changes in the mutation spectrum could arise from viral mutations that affect genome replication, packaging, and antagonization of host innate-immune factors, although environmental factors could also play a role. Interestingly, the mutation spectrum of Omicron is more similar than that of earlier SARS-CoV-2 clades to the spectrum that shaped the long-term evolution of sarbecoviruses. Overall, our work shows that the mutation process is itself a dynamic variable during SARS-CoV-2 evolution and suggests that human SARS-CoV-2 may be trending toward a mutation spectrum more similar to that of other animal sarbecoviruses.",-1),l=[r,n];function c(h,m,u,d,p,f){return o(),a("div",null,l)}const _=t(i,[["render",c]]);export{b as __pageData,_ as default}; +import{_ as t,c as a,o,b as e,d as s}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Evolution of the SARS-CoV-2 mutational spectrum","description":"","frontmatter":{"layout":"paper","title":"Evolution of the SARS-CoV-2 mutational spectrum","date":"2023-04-11","authors":["Jesse D Bloom","Annabel C Beichman","Richard A Neher","Kelley Harris"],"journal":"Molecular Biology and Evolution","doi":"10.1093/molbev/msad085","link":"https://academic.oup.com/mbe/article/40/4/msad085/7113660","image":"/assets/papers/2023_bloom_b.jpg","keywords":["SARS-CoV-2","Phylogenetics"]},"headers":[],"relativePath":"papers/2023_bloom_b.md","filePath":"papers/2023_bloom_b.md"}'),i={name:"papers/2023_bloom_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"SARS-CoV-2 evolves rapidly in part because of its high mutation rate. Here, we examine whether this mutational process itself has changed during viral evolution. To do this, we quantify the relative rates of different types of single-nucleotide mutations at 4-fold degenerate sites in the viral genome across millions of human SARS-CoV-2 sequences. We find clear shifts in the relative rates of several types of mutations during SARS-CoV-2 evolution. The most striking trend is a roughly 2-fold decrease in the relative rate of G→T mutations in Omicron versus early clades, as was recently noted by Ruis et al. (2022. Mutational spectra distinguish SARS-CoV-2 replication niches. bioRxiv, doi:10.1101/2022.09.27.509649). There is also a decrease in the relative rate of C→T mutations in Delta, and other subtle changes in the mutation spectrum along the phylogeny. We speculate that these changes in the mutation spectrum could arise from viral mutations that affect genome replication, packaging, and antagonization of host innate-immune factors, although environmental factors could also play a role. Interestingly, the mutation spectrum of Omicron is more similar than that of earlier SARS-CoV-2 clades to the spectrum that shaped the long-term evolution of sarbecoviruses. Overall, our work shows that the mutation process is itself a dynamic variable during SARS-CoV-2 evolution and suggests that human SARS-CoV-2 may be trending toward a mutation spectrum more similar to that of other animal sarbecoviruses.",-1),l=[r,n];function c(h,m,u,d,p,f){return o(),a("div",null,l)}const _=t(i,[["render",c]]);export{b as __pageData,_ as default}; diff --git a/assets/papers_2023_bloom_b.md.CKQthdh3.lean.js b/assets/papers_2023_bloom_b.md.DAvFQSAm.lean.js similarity index 94% rename from assets/papers_2023_bloom_b.md.CKQthdh3.lean.js rename to assets/papers_2023_bloom_b.md.DAvFQSAm.lean.js index 30a707a..ab32f2d 100644 --- a/assets/papers_2023_bloom_b.md.CKQthdh3.lean.js +++ b/assets/papers_2023_bloom_b.md.DAvFQSAm.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o,b as e,d as s}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Evolution of the SARS-CoV-2 mutational spectrum","description":"","frontmatter":{"layout":"paper","title":"Evolution of the SARS-CoV-2 mutational spectrum","date":"2023-04-11","authors":["Jesse D Bloom","Annabel C Beichman","Richard A Neher","Kelley Harris"],"journal":"Molecular Biology and Evolution","doi":"10.1093/molbev/msad085","link":"https://academic.oup.com/mbe/article/40/4/msad085/7113660","image":"/assets/papers/2023_bloom_b.jpg","keywords":["SARS-CoV-2","Phylogenetics"]},"headers":[],"relativePath":"papers/2023_bloom_b.md","filePath":"papers/2023_bloom_b.md"}'),i={name:"papers/2023_bloom_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"SARS-CoV-2 evolves rapidly in part because of its high mutation rate. Here, we examine whether this mutational process itself has changed during viral evolution. To do this, we quantify the relative rates of different types of single-nucleotide mutations at 4-fold degenerate sites in the viral genome across millions of human SARS-CoV-2 sequences. We find clear shifts in the relative rates of several types of mutations during SARS-CoV-2 evolution. The most striking trend is a roughly 2-fold decrease in the relative rate of G→T mutations in Omicron versus early clades, as was recently noted by Ruis et al. (2022. Mutational spectra distinguish SARS-CoV-2 replication niches. bioRxiv, doi:10.1101/2022.09.27.509649). There is also a decrease in the relative rate of C→T mutations in Delta, and other subtle changes in the mutation spectrum along the phylogeny. We speculate that these changes in the mutation spectrum could arise from viral mutations that affect genome replication, packaging, and antagonization of host innate-immune factors, although environmental factors could also play a role. Interestingly, the mutation spectrum of Omicron is more similar than that of earlier SARS-CoV-2 clades to the spectrum that shaped the long-term evolution of sarbecoviruses. Overall, our work shows that the mutation process is itself a dynamic variable during SARS-CoV-2 evolution and suggests that human SARS-CoV-2 may be trending toward a mutation spectrum more similar to that of other animal sarbecoviruses.",-1),l=[r,n];function c(h,m,u,d,p,f){return o(),a("div",null,l)}const _=t(i,[["render",c]]);export{b as __pageData,_ as default}; +import{_ as t,c as a,o,b as e,d as s}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Evolution of the SARS-CoV-2 mutational spectrum","description":"","frontmatter":{"layout":"paper","title":"Evolution of the SARS-CoV-2 mutational spectrum","date":"2023-04-11","authors":["Jesse D Bloom","Annabel C Beichman","Richard A Neher","Kelley Harris"],"journal":"Molecular Biology and Evolution","doi":"10.1093/molbev/msad085","link":"https://academic.oup.com/mbe/article/40/4/msad085/7113660","image":"/assets/papers/2023_bloom_b.jpg","keywords":["SARS-CoV-2","Phylogenetics"]},"headers":[],"relativePath":"papers/2023_bloom_b.md","filePath":"papers/2023_bloom_b.md"}'),i={name:"papers/2023_bloom_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"SARS-CoV-2 evolves rapidly in part because of its high mutation rate. Here, we examine whether this mutational process itself has changed during viral evolution. To do this, we quantify the relative rates of different types of single-nucleotide mutations at 4-fold degenerate sites in the viral genome across millions of human SARS-CoV-2 sequences. We find clear shifts in the relative rates of several types of mutations during SARS-CoV-2 evolution. The most striking trend is a roughly 2-fold decrease in the relative rate of G→T mutations in Omicron versus early clades, as was recently noted by Ruis et al. (2022. Mutational spectra distinguish SARS-CoV-2 replication niches. bioRxiv, doi:10.1101/2022.09.27.509649). There is also a decrease in the relative rate of C→T mutations in Delta, and other subtle changes in the mutation spectrum along the phylogeny. We speculate that these changes in the mutation spectrum could arise from viral mutations that affect genome replication, packaging, and antagonization of host innate-immune factors, although environmental factors could also play a role. Interestingly, the mutation spectrum of Omicron is more similar than that of earlier SARS-CoV-2 clades to the spectrum that shaped the long-term evolution of sarbecoviruses. Overall, our work shows that the mutation process is itself a dynamic variable during SARS-CoV-2 evolution and suggests that human SARS-CoV-2 may be trending toward a mutation spectrum more similar to that of other animal sarbecoviruses.",-1),l=[r,n];function c(h,m,u,d,p,f){return o(),a("div",null,l)}const _=t(i,[["render",c]]);export{b as __pageData,_ as default}; diff --git a/assets/papers_2023_bloom_c.md.wbMHRRqa.js b/assets/papers_2023_bloom_c.md.YecZKxe_.js similarity index 97% rename from assets/papers_2023_bloom_c.md.wbMHRRqa.js rename to assets/papers_2023_bloom_c.md.YecZKxe_.js index 455fe5a..778fe93 100644 --- a/assets/papers_2023_bloom_c.md.wbMHRRqa.js +++ b/assets/papers_2023_bloom_c.md.YecZKxe_.js @@ -1 +1 @@ -import{_ as o,c as a,o as s,b as e,d as t}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Fitness effects of mutations to SARS-CoV-2 proteins","description":"","frontmatter":{"layout":"paper","title":"Fitness effects of mutations to SARS-CoV-2 proteins","date":"2023-09-18","authors":["Jesse D Bloom","Richard A Neher"],"journal":"Virus Evolution","doi":"10.1093/ve/veae026","link":"https://academic.oup.com/ve/article/9/2/vead055/7265011","image":"/assets/papers/2023_bloom_c.jpg","selected":true,"keywords":["SARS-CoV-2","Phylogenetics"]},"headers":[],"relativePath":"papers/2023_bloom_c.md","filePath":"papers/2023_bloom_c.md"}'),n={name:"papers/2023_bloom_c.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,[t("Knowledge of the fitness effects of mutations to SARS-CoV-2 can inform assessment of new variants, design of therapeutics resistant to escape, and understanding of the functions of viral proteins. However, experimentally measuring effects of mutations is challenging: we lack tractable lab assays for many SARS-CoV-2 proteins, and comprehensive deep mutational scanning has been applied to only two SARS-CoV-2 proteins. Here, we develop an approach that leverages millions of publicly available SARS-CoV-2 sequences to estimate effects of mutations. We first calculate how many independent occurrences of each mutation are expected to be observed along the SARS-CoV-2 phylogeny in the absence of selection. We then compare these expected observations to the actual observations to estimate the effect of each mutation. These estimates correlate well with deep mutational scanning measurements. For most genes, synonymous mutations are nearly neutral, stop-codon mutations are deleterious, and amino acid mutations have a range of effects. However, some viral accessory proteins are under little to no selection. We provide interactive visualizations of effects of mutations to all SARS-CoV-2 proteins ("),e("a",{href:"https://jbloomlab.github.io/SARS2-mut-fitness/",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/SARS2-mut-fitness/"),t("). The framework we describe is applicable to any virus for which the number of available sequences is sufficiently large that many independent occurrences of each neutral mutation are observed.")],-1),c=[i,r];function l(m,f,p,u,d,h){return s(),a("div",null,c)}const v=o(n,[["render",l]]);export{_ as __pageData,v as default}; +import{_ as o,c as a,o as s,b as e,d as t}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Fitness effects of mutations to SARS-CoV-2 proteins","description":"","frontmatter":{"layout":"paper","title":"Fitness effects of mutations to SARS-CoV-2 proteins","date":"2023-09-18","authors":["Jesse D Bloom","Richard A Neher"],"journal":"Virus Evolution","doi":"10.1093/ve/veae026","link":"https://academic.oup.com/ve/article/9/2/vead055/7265011","image":"/assets/papers/2023_bloom_c.jpg","selected":true,"keywords":["SARS-CoV-2","Phylogenetics"]},"headers":[],"relativePath":"papers/2023_bloom_c.md","filePath":"papers/2023_bloom_c.md"}'),n={name:"papers/2023_bloom_c.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,[t("Knowledge of the fitness effects of mutations to SARS-CoV-2 can inform assessment of new variants, design of therapeutics resistant to escape, and understanding of the functions of viral proteins. However, experimentally measuring effects of mutations is challenging: we lack tractable lab assays for many SARS-CoV-2 proteins, and comprehensive deep mutational scanning has been applied to only two SARS-CoV-2 proteins. Here, we develop an approach that leverages millions of publicly available SARS-CoV-2 sequences to estimate effects of mutations. We first calculate how many independent occurrences of each mutation are expected to be observed along the SARS-CoV-2 phylogeny in the absence of selection. We then compare these expected observations to the actual observations to estimate the effect of each mutation. These estimates correlate well with deep mutational scanning measurements. For most genes, synonymous mutations are nearly neutral, stop-codon mutations are deleterious, and amino acid mutations have a range of effects. However, some viral accessory proteins are under little to no selection. We provide interactive visualizations of effects of mutations to all SARS-CoV-2 proteins ("),e("a",{href:"https://jbloomlab.github.io/SARS2-mut-fitness/",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/SARS2-mut-fitness/"),t("). The framework we describe is applicable to any virus for which the number of available sequences is sufficiently large that many independent occurrences of each neutral mutation are observed.")],-1),c=[i,r];function l(m,f,p,u,d,h){return s(),a("div",null,c)}const v=o(n,[["render",l]]);export{_ as __pageData,v as default}; diff --git a/assets/papers_2023_bloom_c.md.wbMHRRqa.lean.js b/assets/papers_2023_bloom_c.md.YecZKxe_.lean.js similarity index 97% rename from assets/papers_2023_bloom_c.md.wbMHRRqa.lean.js rename to assets/papers_2023_bloom_c.md.YecZKxe_.lean.js index 455fe5a..778fe93 100644 --- a/assets/papers_2023_bloom_c.md.wbMHRRqa.lean.js +++ b/assets/papers_2023_bloom_c.md.YecZKxe_.lean.js @@ -1 +1 @@ -import{_ as o,c as a,o as s,b as e,d as t}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Fitness effects of mutations to SARS-CoV-2 proteins","description":"","frontmatter":{"layout":"paper","title":"Fitness effects of mutations to SARS-CoV-2 proteins","date":"2023-09-18","authors":["Jesse D Bloom","Richard A Neher"],"journal":"Virus Evolution","doi":"10.1093/ve/veae026","link":"https://academic.oup.com/ve/article/9/2/vead055/7265011","image":"/assets/papers/2023_bloom_c.jpg","selected":true,"keywords":["SARS-CoV-2","Phylogenetics"]},"headers":[],"relativePath":"papers/2023_bloom_c.md","filePath":"papers/2023_bloom_c.md"}'),n={name:"papers/2023_bloom_c.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,[t("Knowledge of the fitness effects of mutations to SARS-CoV-2 can inform assessment of new variants, design of therapeutics resistant to escape, and understanding of the functions of viral proteins. However, experimentally measuring effects of mutations is challenging: we lack tractable lab assays for many SARS-CoV-2 proteins, and comprehensive deep mutational scanning has been applied to only two SARS-CoV-2 proteins. Here, we develop an approach that leverages millions of publicly available SARS-CoV-2 sequences to estimate effects of mutations. We first calculate how many independent occurrences of each mutation are expected to be observed along the SARS-CoV-2 phylogeny in the absence of selection. We then compare these expected observations to the actual observations to estimate the effect of each mutation. These estimates correlate well with deep mutational scanning measurements. For most genes, synonymous mutations are nearly neutral, stop-codon mutations are deleterious, and amino acid mutations have a range of effects. However, some viral accessory proteins are under little to no selection. We provide interactive visualizations of effects of mutations to all SARS-CoV-2 proteins ("),e("a",{href:"https://jbloomlab.github.io/SARS2-mut-fitness/",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/SARS2-mut-fitness/"),t("). The framework we describe is applicable to any virus for which the number of available sequences is sufficiently large that many independent occurrences of each neutral mutation are observed.")],-1),c=[i,r];function l(m,f,p,u,d,h){return s(),a("div",null,c)}const v=o(n,[["render",l]]);export{_ as __pageData,v as default}; +import{_ as o,c as a,o as s,b as e,d as t}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Fitness effects of mutations to SARS-CoV-2 proteins","description":"","frontmatter":{"layout":"paper","title":"Fitness effects of mutations to SARS-CoV-2 proteins","date":"2023-09-18","authors":["Jesse D Bloom","Richard A Neher"],"journal":"Virus Evolution","doi":"10.1093/ve/veae026","link":"https://academic.oup.com/ve/article/9/2/vead055/7265011","image":"/assets/papers/2023_bloom_c.jpg","selected":true,"keywords":["SARS-CoV-2","Phylogenetics"]},"headers":[],"relativePath":"papers/2023_bloom_c.md","filePath":"papers/2023_bloom_c.md"}'),n={name:"papers/2023_bloom_c.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,[t("Knowledge of the fitness effects of mutations to SARS-CoV-2 can inform assessment of new variants, design of therapeutics resistant to escape, and understanding of the functions of viral proteins. However, experimentally measuring effects of mutations is challenging: we lack tractable lab assays for many SARS-CoV-2 proteins, and comprehensive deep mutational scanning has been applied to only two SARS-CoV-2 proteins. Here, we develop an approach that leverages millions of publicly available SARS-CoV-2 sequences to estimate effects of mutations. We first calculate how many independent occurrences of each mutation are expected to be observed along the SARS-CoV-2 phylogeny in the absence of selection. We then compare these expected observations to the actual observations to estimate the effect of each mutation. These estimates correlate well with deep mutational scanning measurements. For most genes, synonymous mutations are nearly neutral, stop-codon mutations are deleterious, and amino acid mutations have a range of effects. However, some viral accessory proteins are under little to no selection. We provide interactive visualizations of effects of mutations to all SARS-CoV-2 proteins ("),e("a",{href:"https://jbloomlab.github.io/SARS2-mut-fitness/",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/SARS2-mut-fitness/"),t("). The framework we describe is applicable to any virus for which the number of available sequences is sufficiently large that many independent occurrences of each neutral mutation are observed.")],-1),c=[i,r];function l(m,f,p,u,d,h){return s(),a("div",null,c)}const v=o(n,[["render",l]]);export{_ as __pageData,v as default}; diff --git a/assets/papers_2023_dadonaite_crawford_radford.md.BDjcLbtk.js b/assets/papers_2023_dadonaite_crawford_radford.md.CjEimFsm.js similarity index 97% rename from assets/papers_2023_dadonaite_crawford_radford.md.BDjcLbtk.js rename to assets/papers_2023_dadonaite_crawford_radford.md.CjEimFsm.js index 3929e84..60a5784 100644 --- a/assets/papers_2023_dadonaite_crawford_radford.md.BDjcLbtk.js +++ b/assets/papers_2023_dadonaite_crawford_radford.md.CjEimFsm.js @@ -1 +1 @@ -import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike","description":"","frontmatter":{"layout":"paper","title":"A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike","date":"2023-03-16","authors":["Bernadeta Dadonaite*","Katharine HD Crawford*","Caelan E Radford*","Ariana G Farrell","C Yu Timothy","William W Hannon","Panpan Zhou","Raiees Andrabi","Dennis R Burton","Lihong Liu","David D Ho","Helen Y Chu","Richard A Neher","Jesse D Bloom"],"journal":"Cell","doi":"10.1016/j.cell.2023.02.001","link":"https://www.cell.com/cell/pdf/S0092-8674(23)00103-4.pdf","image":"/assets/papers/2023_dadonaite_crawford_radford.png","keywords":["SARS-CoV-2","Deep mutational scanning","Pseudovirus"],"selected":true},"headers":[],"relativePath":"papers/2023_dadonaite_crawford_radford.md","filePath":"papers/2023_dadonaite_crawford_radford.md"}'),o={name:"papers/2023_dadonaite_crawford_radford.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"A major challenge in understanding SARS-CoV-2 evolution is interpreting the antigenic and functional effects of emerging mutations in the viral spike protein. Here, we describe a deep mutational scanning platform based on non-replicative pseudotyped lentiviruses that directly quantifies how large numbers of spike mutations impact antibody neutralization and pseudovirus infection. We apply this platform to produce libraries of the Omicron BA.1 and Delta spikes. These libraries each contain ∼7,000 distinct amino acid mutations in the context of up to ∼135,000 unique mutation combinations. We use these libraries to map escape mutations from neutralizing antibodies targeting the receptor-binding domain, N-terminal domain, and S2 subunit of spike. Overall, this work establishes a high-throughput and safe approach to measure how ∼105 combinations of mutations affect antibody neutralization and spike-mediated infection. Notably, the platform described here can be extended to the entry proteins of many other viruses.",-1),d=[r,s];function l(c,p,u,f,h,m){return n(),t("div",null,d)}const g=a(o,[["render",l]]);export{b as __pageData,g as default}; +import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike","description":"","frontmatter":{"layout":"paper","title":"A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike","date":"2023-03-16","authors":["Bernadeta Dadonaite*","Katharine HD Crawford*","Caelan E Radford*","Ariana G Farrell","C Yu Timothy","William W Hannon","Panpan Zhou","Raiees Andrabi","Dennis R Burton","Lihong Liu","David D Ho","Helen Y Chu","Richard A Neher","Jesse D Bloom"],"journal":"Cell","doi":"10.1016/j.cell.2023.02.001","link":"https://www.cell.com/cell/pdf/S0092-8674(23)00103-4.pdf","image":"/assets/papers/2023_dadonaite_crawford_radford.png","keywords":["SARS-CoV-2","Deep mutational scanning","Pseudovirus"],"selected":true},"headers":[],"relativePath":"papers/2023_dadonaite_crawford_radford.md","filePath":"papers/2023_dadonaite_crawford_radford.md"}'),o={name:"papers/2023_dadonaite_crawford_radford.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"A major challenge in understanding SARS-CoV-2 evolution is interpreting the antigenic and functional effects of emerging mutations in the viral spike protein. Here, we describe a deep mutational scanning platform based on non-replicative pseudotyped lentiviruses that directly quantifies how large numbers of spike mutations impact antibody neutralization and pseudovirus infection. We apply this platform to produce libraries of the Omicron BA.1 and Delta spikes. These libraries each contain ∼7,000 distinct amino acid mutations in the context of up to ∼135,000 unique mutation combinations. We use these libraries to map escape mutations from neutralizing antibodies targeting the receptor-binding domain, N-terminal domain, and S2 subunit of spike. Overall, this work establishes a high-throughput and safe approach to measure how ∼105 combinations of mutations affect antibody neutralization and spike-mediated infection. Notably, the platform described here can be extended to the entry proteins of many other viruses.",-1),d=[r,s];function l(c,p,u,f,h,m){return n(),t("div",null,d)}const g=a(o,[["render",l]]);export{b as __pageData,g as default}; diff --git a/assets/papers_2023_dadonaite_crawford_radford.md.BDjcLbtk.lean.js b/assets/papers_2023_dadonaite_crawford_radford.md.CjEimFsm.lean.js similarity index 97% rename from assets/papers_2023_dadonaite_crawford_radford.md.BDjcLbtk.lean.js rename to assets/papers_2023_dadonaite_crawford_radford.md.CjEimFsm.lean.js index 3929e84..60a5784 100644 --- a/assets/papers_2023_dadonaite_crawford_radford.md.BDjcLbtk.lean.js +++ b/assets/papers_2023_dadonaite_crawford_radford.md.CjEimFsm.lean.js @@ -1 +1 @@ -import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike","description":"","frontmatter":{"layout":"paper","title":"A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike","date":"2023-03-16","authors":["Bernadeta Dadonaite*","Katharine HD Crawford*","Caelan E Radford*","Ariana G Farrell","C Yu Timothy","William W Hannon","Panpan Zhou","Raiees Andrabi","Dennis R Burton","Lihong Liu","David D Ho","Helen Y Chu","Richard A Neher","Jesse D Bloom"],"journal":"Cell","doi":"10.1016/j.cell.2023.02.001","link":"https://www.cell.com/cell/pdf/S0092-8674(23)00103-4.pdf","image":"/assets/papers/2023_dadonaite_crawford_radford.png","keywords":["SARS-CoV-2","Deep mutational scanning","Pseudovirus"],"selected":true},"headers":[],"relativePath":"papers/2023_dadonaite_crawford_radford.md","filePath":"papers/2023_dadonaite_crawford_radford.md"}'),o={name:"papers/2023_dadonaite_crawford_radford.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"A major challenge in understanding SARS-CoV-2 evolution is interpreting the antigenic and functional effects of emerging mutations in the viral spike protein. Here, we describe a deep mutational scanning platform based on non-replicative pseudotyped lentiviruses that directly quantifies how large numbers of spike mutations impact antibody neutralization and pseudovirus infection. We apply this platform to produce libraries of the Omicron BA.1 and Delta spikes. These libraries each contain ∼7,000 distinct amino acid mutations in the context of up to ∼135,000 unique mutation combinations. We use these libraries to map escape mutations from neutralizing antibodies targeting the receptor-binding domain, N-terminal domain, and S2 subunit of spike. Overall, this work establishes a high-throughput and safe approach to measure how ∼105 combinations of mutations affect antibody neutralization and spike-mediated infection. Notably, the platform described here can be extended to the entry proteins of many other viruses.",-1),d=[r,s];function l(c,p,u,f,h,m){return n(),t("div",null,d)}const g=a(o,[["render",l]]);export{b as __pageData,g as default}; +import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike","description":"","frontmatter":{"layout":"paper","title":"A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike","date":"2023-03-16","authors":["Bernadeta Dadonaite*","Katharine HD Crawford*","Caelan E Radford*","Ariana G Farrell","C Yu Timothy","William W Hannon","Panpan Zhou","Raiees Andrabi","Dennis R Burton","Lihong Liu","David D Ho","Helen Y Chu","Richard A Neher","Jesse D Bloom"],"journal":"Cell","doi":"10.1016/j.cell.2023.02.001","link":"https://www.cell.com/cell/pdf/S0092-8674(23)00103-4.pdf","image":"/assets/papers/2023_dadonaite_crawford_radford.png","keywords":["SARS-CoV-2","Deep mutational scanning","Pseudovirus"],"selected":true},"headers":[],"relativePath":"papers/2023_dadonaite_crawford_radford.md","filePath":"papers/2023_dadonaite_crawford_radford.md"}'),o={name:"papers/2023_dadonaite_crawford_radford.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"A major challenge in understanding SARS-CoV-2 evolution is interpreting the antigenic and functional effects of emerging mutations in the viral spike protein. Here, we describe a deep mutational scanning platform based on non-replicative pseudotyped lentiviruses that directly quantifies how large numbers of spike mutations impact antibody neutralization and pseudovirus infection. We apply this platform to produce libraries of the Omicron BA.1 and Delta spikes. These libraries each contain ∼7,000 distinct amino acid mutations in the context of up to ∼135,000 unique mutation combinations. We use these libraries to map escape mutations from neutralizing antibodies targeting the receptor-binding domain, N-terminal domain, and S2 subunit of spike. Overall, this work establishes a high-throughput and safe approach to measure how ∼105 combinations of mutations affect antibody neutralization and spike-mediated infection. Notably, the platform described here can be extended to the entry proteins of many other viruses.",-1),d=[r,s];function l(c,p,u,f,h,m){return n(),t("div",null,d)}const g=a(o,[["render",l]]);export{b as __pageData,g as default}; diff --git a/assets/papers_2023_kikawa.md.CouKrgrY.js b/assets/papers_2023_kikawa.md.sK6GyFCo.js similarity index 97% rename from assets/papers_2023_kikawa.md.CouKrgrY.js rename to assets/papers_2023_kikawa.md.sK6GyFCo.js index 017f97a..72497ec 100644 --- a/assets/papers_2023_kikawa.md.CouKrgrY.js +++ b/assets/papers_2023_kikawa.md.sK6GyFCo.js @@ -1 +1 @@ -import{_ as a,c as i,o as t,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const m=JSON.parse('{"title":"The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies","description":"","frontmatter":{"layout":"paper","title":"The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies","date":"2023-11-30","authors":["Caroline Kikawa","Catiana H Cartwright-Acar","Jackson B Stuart","Maya Contreras","Lisa M Levoir","Matthew J Evans","Jesse D Bloom","Leslie Goo"],"journal":"Journal of Virology","doi":"10.1128/jvi.01414-23","link":"https://journals.asm.org/doi/full/10.1128/jvi.01414-23","image":"/assets/papers/2023_kikawa.jpg","keywords":["Zika","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2023_kikawa.md","filePath":"papers/2023_kikawa.md"}'),o={name:"papers/2023_kikawa.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Zika virus and dengue virus are co-circulating flaviviruses with a widespread endemic range. Eliciting broad and potent neutralizing antibodies is an attractive goal for developing a vaccine to simultaneously protect against these viruses. However, the capacity of viral mutations to confer escape from broadly neutralizing antibodies remains undescribed, due in part to limited throughput and scope of traditional approaches. Here, we use deep mutational scanning to map how all possible single amino acid mutations in Zika virus envelope protein affect neutralization by antibodies of varying breadth and potency. While all antibodies selected viral escape mutations, the mutations selected by broadly neutralizing antibodies conferred less escape relative to those selected by narrow, virus-specific antibodies. Surprisingly, even for broadly neutralizing antibodies with similar binding footprints, different single mutations led to escape, indicating distinct functional requirements for neutralization not captured by existing structures. Additionally, the antigenic effects of mutations selected by broadly neutralizing antibodies were conserved across divergent, albeit related, flaviviruses. Our approach identifies residues critical for antibody neutralization, thus comprehensively defining the as-yet-unknown functional epitopes of antibodies with clinical potential.",-1),l=[s,r];function c(d,u,p,f,b,g){return t(),i("div",null,l)}const v=a(o,[["render",c]]);export{m as __pageData,v as default}; +import{_ as a,c as i,o as t,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const m=JSON.parse('{"title":"The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies","description":"","frontmatter":{"layout":"paper","title":"The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies","date":"2023-11-30","authors":["Caroline Kikawa","Catiana H Cartwright-Acar","Jackson B Stuart","Maya Contreras","Lisa M Levoir","Matthew J Evans","Jesse D Bloom","Leslie Goo"],"journal":"Journal of Virology","doi":"10.1128/jvi.01414-23","link":"https://journals.asm.org/doi/full/10.1128/jvi.01414-23","image":"/assets/papers/2023_kikawa.jpg","keywords":["Zika","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2023_kikawa.md","filePath":"papers/2023_kikawa.md"}'),o={name:"papers/2023_kikawa.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Zika virus and dengue virus are co-circulating flaviviruses with a widespread endemic range. Eliciting broad and potent neutralizing antibodies is an attractive goal for developing a vaccine to simultaneously protect against these viruses. However, the capacity of viral mutations to confer escape from broadly neutralizing antibodies remains undescribed, due in part to limited throughput and scope of traditional approaches. Here, we use deep mutational scanning to map how all possible single amino acid mutations in Zika virus envelope protein affect neutralization by antibodies of varying breadth and potency. While all antibodies selected viral escape mutations, the mutations selected by broadly neutralizing antibodies conferred less escape relative to those selected by narrow, virus-specific antibodies. Surprisingly, even for broadly neutralizing antibodies with similar binding footprints, different single mutations led to escape, indicating distinct functional requirements for neutralization not captured by existing structures. Additionally, the antigenic effects of mutations selected by broadly neutralizing antibodies were conserved across divergent, albeit related, flaviviruses. Our approach identifies residues critical for antibody neutralization, thus comprehensively defining the as-yet-unknown functional epitopes of antibodies with clinical potential.",-1),l=[s,r];function c(d,u,p,f,b,g){return t(),i("div",null,l)}const v=a(o,[["render",c]]);export{m as __pageData,v as default}; diff --git a/assets/papers_2023_kikawa.md.CouKrgrY.lean.js b/assets/papers_2023_kikawa.md.sK6GyFCo.lean.js similarity index 97% rename from assets/papers_2023_kikawa.md.CouKrgrY.lean.js rename to assets/papers_2023_kikawa.md.sK6GyFCo.lean.js index 017f97a..72497ec 100644 --- a/assets/papers_2023_kikawa.md.CouKrgrY.lean.js +++ b/assets/papers_2023_kikawa.md.sK6GyFCo.lean.js @@ -1 +1 @@ -import{_ as a,c as i,o as t,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const m=JSON.parse('{"title":"The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies","description":"","frontmatter":{"layout":"paper","title":"The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies","date":"2023-11-30","authors":["Caroline Kikawa","Catiana H Cartwright-Acar","Jackson B Stuart","Maya Contreras","Lisa M Levoir","Matthew J Evans","Jesse D Bloom","Leslie Goo"],"journal":"Journal of Virology","doi":"10.1128/jvi.01414-23","link":"https://journals.asm.org/doi/full/10.1128/jvi.01414-23","image":"/assets/papers/2023_kikawa.jpg","keywords":["Zika","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2023_kikawa.md","filePath":"papers/2023_kikawa.md"}'),o={name:"papers/2023_kikawa.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Zika virus and dengue virus are co-circulating flaviviruses with a widespread endemic range. Eliciting broad and potent neutralizing antibodies is an attractive goal for developing a vaccine to simultaneously protect against these viruses. However, the capacity of viral mutations to confer escape from broadly neutralizing antibodies remains undescribed, due in part to limited throughput and scope of traditional approaches. Here, we use deep mutational scanning to map how all possible single amino acid mutations in Zika virus envelope protein affect neutralization by antibodies of varying breadth and potency. While all antibodies selected viral escape mutations, the mutations selected by broadly neutralizing antibodies conferred less escape relative to those selected by narrow, virus-specific antibodies. Surprisingly, even for broadly neutralizing antibodies with similar binding footprints, different single mutations led to escape, indicating distinct functional requirements for neutralization not captured by existing structures. Additionally, the antigenic effects of mutations selected by broadly neutralizing antibodies were conserved across divergent, albeit related, flaviviruses. Our approach identifies residues critical for antibody neutralization, thus comprehensively defining the as-yet-unknown functional epitopes of antibodies with clinical potential.",-1),l=[s,r];function c(d,u,p,f,b,g){return t(),i("div",null,l)}const v=a(o,[["render",c]]);export{m as __pageData,v as default}; +import{_ as a,c as i,o as t,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const m=JSON.parse('{"title":"The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies","description":"","frontmatter":{"layout":"paper","title":"The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies","date":"2023-11-30","authors":["Caroline Kikawa","Catiana H Cartwright-Acar","Jackson B Stuart","Maya Contreras","Lisa M Levoir","Matthew J Evans","Jesse D Bloom","Leslie Goo"],"journal":"Journal of Virology","doi":"10.1128/jvi.01414-23","link":"https://journals.asm.org/doi/full/10.1128/jvi.01414-23","image":"/assets/papers/2023_kikawa.jpg","keywords":["Zika","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2023_kikawa.md","filePath":"papers/2023_kikawa.md"}'),o={name:"papers/2023_kikawa.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Zika virus and dengue virus are co-circulating flaviviruses with a widespread endemic range. Eliciting broad and potent neutralizing antibodies is an attractive goal for developing a vaccine to simultaneously protect against these viruses. However, the capacity of viral mutations to confer escape from broadly neutralizing antibodies remains undescribed, due in part to limited throughput and scope of traditional approaches. Here, we use deep mutational scanning to map how all possible single amino acid mutations in Zika virus envelope protein affect neutralization by antibodies of varying breadth and potency. While all antibodies selected viral escape mutations, the mutations selected by broadly neutralizing antibodies conferred less escape relative to those selected by narrow, virus-specific antibodies. Surprisingly, even for broadly neutralizing antibodies with similar binding footprints, different single mutations led to escape, indicating distinct functional requirements for neutralization not captured by existing structures. Additionally, the antigenic effects of mutations selected by broadly neutralizing antibodies were conserved across divergent, albeit related, flaviviruses. Our approach identifies residues critical for antibody neutralization, thus comprehensively defining the as-yet-unknown functional epitopes of antibodies with clinical potential.",-1),l=[s,r];function c(d,u,p,f,b,g){return t(),i("div",null,l)}const v=a(o,[["render",c]]);export{m as __pageData,v as default}; diff --git a/assets/papers_2023_radford.md.CXxkiNGY.js b/assets/papers_2023_radford.md.C_kQNWwR.js similarity index 97% rename from assets/papers_2023_radford.md.CXxkiNGY.js rename to assets/papers_2023_radford.md.C_kQNWwR.js index 6bef0ff..9500fd2 100644 --- a/assets/papers_2023_radford.md.CXxkiNGY.js +++ b/assets/papers_2023_radford.md.C_kQNWwR.js @@ -1 +1 @@ -import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning","description":"","frontmatter":{"layout":"paper","title":"Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning","date":"2023-07-12","authors":["Caelan E Radford","Philipp Schommers","Lutz Gieselmann","Katharine HD Crawford","Bernadeta Dadonaite","Timothy C Yu","Adam S Dingens","Julie Overbaugh","Florian Klein","Jesse D Bloom"],"journal":"Cell Host & Microbe","doi":"10.1016/j.chom.2023.05.025","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(23)00218-4.pdf","image":"/assets/papers/2023_radford.png","keywords":["HIV","Deep mutational scanning","Pseudovirus"]},"headers":[],"relativePath":"papers/2023_radford.md","filePath":"papers/2023_radford.md"}'),s={name:"papers/2023_radford.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Understanding the specificities of human serum antibodies that broadly neutralize HIV can inform prevention and treatment strategies. Here, we describe a deep mutational scanning system that can measure the effects of combinations of mutations to HIV envelope (Env) on neutralization by antibodies and polyclonal serum. We first show that this system can accurately map how all functionally tolerated mutations to Env affect neutralization by monoclonal antibodies. We then comprehensively map Env mutations that affect neutralization by a set of human polyclonal sera that neutralize diverse strains of HIV and target the site engaging the host receptor CD4. The neutralizing activities of these sera target different epitopes, with most sera having specificities reminiscent of individual characterized monoclonal antibodies, but one serum targeting two epitopes within the CD4-binding site. Mapping the specificity of the neutralizing activity in polyclonal human serum will aid in assessing anti-HIV immune responses to inform prevention strategies.",-1),c=[o,r];function l(d,p,m,h,u,f){return i(),a("div",null,c)}const _=t(s,[["render",l]]);export{b as __pageData,_ as default}; +import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning","description":"","frontmatter":{"layout":"paper","title":"Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning","date":"2023-07-12","authors":["Caelan E Radford","Philipp Schommers","Lutz Gieselmann","Katharine HD Crawford","Bernadeta Dadonaite","Timothy C Yu","Adam S Dingens","Julie Overbaugh","Florian Klein","Jesse D Bloom"],"journal":"Cell Host & Microbe","doi":"10.1016/j.chom.2023.05.025","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(23)00218-4.pdf","image":"/assets/papers/2023_radford.png","keywords":["HIV","Deep mutational scanning","Pseudovirus"]},"headers":[],"relativePath":"papers/2023_radford.md","filePath":"papers/2023_radford.md"}'),s={name:"papers/2023_radford.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Understanding the specificities of human serum antibodies that broadly neutralize HIV can inform prevention and treatment strategies. Here, we describe a deep mutational scanning system that can measure the effects of combinations of mutations to HIV envelope (Env) on neutralization by antibodies and polyclonal serum. We first show that this system can accurately map how all functionally tolerated mutations to Env affect neutralization by monoclonal antibodies. We then comprehensively map Env mutations that affect neutralization by a set of human polyclonal sera that neutralize diverse strains of HIV and target the site engaging the host receptor CD4. The neutralizing activities of these sera target different epitopes, with most sera having specificities reminiscent of individual characterized monoclonal antibodies, but one serum targeting two epitopes within the CD4-binding site. Mapping the specificity of the neutralizing activity in polyclonal human serum will aid in assessing anti-HIV immune responses to inform prevention strategies.",-1),c=[o,r];function l(d,p,m,h,u,f){return i(),a("div",null,c)}const _=t(s,[["render",l]]);export{b as __pageData,_ as default}; diff --git a/assets/papers_2023_radford.md.CXxkiNGY.lean.js b/assets/papers_2023_radford.md.C_kQNWwR.lean.js similarity index 97% rename from assets/papers_2023_radford.md.CXxkiNGY.lean.js rename to assets/papers_2023_radford.md.C_kQNWwR.lean.js index 6bef0ff..9500fd2 100644 --- a/assets/papers_2023_radford.md.CXxkiNGY.lean.js +++ b/assets/papers_2023_radford.md.C_kQNWwR.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning","description":"","frontmatter":{"layout":"paper","title":"Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning","date":"2023-07-12","authors":["Caelan E Radford","Philipp Schommers","Lutz Gieselmann","Katharine HD Crawford","Bernadeta Dadonaite","Timothy C Yu","Adam S Dingens","Julie Overbaugh","Florian Klein","Jesse D Bloom"],"journal":"Cell Host & Microbe","doi":"10.1016/j.chom.2023.05.025","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(23)00218-4.pdf","image":"/assets/papers/2023_radford.png","keywords":["HIV","Deep mutational scanning","Pseudovirus"]},"headers":[],"relativePath":"papers/2023_radford.md","filePath":"papers/2023_radford.md"}'),s={name:"papers/2023_radford.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Understanding the specificities of human serum antibodies that broadly neutralize HIV can inform prevention and treatment strategies. Here, we describe a deep mutational scanning system that can measure the effects of combinations of mutations to HIV envelope (Env) on neutralization by antibodies and polyclonal serum. We first show that this system can accurately map how all functionally tolerated mutations to Env affect neutralization by monoclonal antibodies. We then comprehensively map Env mutations that affect neutralization by a set of human polyclonal sera that neutralize diverse strains of HIV and target the site engaging the host receptor CD4. The neutralizing activities of these sera target different epitopes, with most sera having specificities reminiscent of individual characterized monoclonal antibodies, but one serum targeting two epitopes within the CD4-binding site. Mapping the specificity of the neutralizing activity in polyclonal human serum will aid in assessing anti-HIV immune responses to inform prevention strategies.",-1),c=[o,r];function l(d,p,m,h,u,f){return i(),a("div",null,c)}const _=t(s,[["render",l]]);export{b as __pageData,_ as default}; +import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning","description":"","frontmatter":{"layout":"paper","title":"Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning","date":"2023-07-12","authors":["Caelan E Radford","Philipp Schommers","Lutz Gieselmann","Katharine HD Crawford","Bernadeta Dadonaite","Timothy C Yu","Adam S Dingens","Julie Overbaugh","Florian Klein","Jesse D Bloom"],"journal":"Cell Host & Microbe","doi":"10.1016/j.chom.2023.05.025","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(23)00218-4.pdf","image":"/assets/papers/2023_radford.png","keywords":["HIV","Deep mutational scanning","Pseudovirus"]},"headers":[],"relativePath":"papers/2023_radford.md","filePath":"papers/2023_radford.md"}'),s={name:"papers/2023_radford.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Understanding the specificities of human serum antibodies that broadly neutralize HIV can inform prevention and treatment strategies. Here, we describe a deep mutational scanning system that can measure the effects of combinations of mutations to HIV envelope (Env) on neutralization by antibodies and polyclonal serum. We first show that this system can accurately map how all functionally tolerated mutations to Env affect neutralization by monoclonal antibodies. We then comprehensively map Env mutations that affect neutralization by a set of human polyclonal sera that neutralize diverse strains of HIV and target the site engaging the host receptor CD4. The neutralizing activities of these sera target different epitopes, with most sera having specificities reminiscent of individual characterized monoclonal antibodies, but one serum targeting two epitopes within the CD4-binding site. Mapping the specificity of the neutralizing activity in polyclonal human serum will aid in assessing anti-HIV immune responses to inform prevention strategies.",-1),c=[o,r];function l(d,p,m,h,u,f){return i(),a("div",null,c)}const _=t(s,[["render",l]]);export{b as __pageData,_ as default}; diff --git a/assets/papers_2024_bloom.md.DFgYCwvg.js b/assets/papers_2024_bloom.md.BKiXUzLp.js similarity index 97% rename from assets/papers_2024_bloom.md.DFgYCwvg.js rename to assets/papers_2024_bloom.md.BKiXUzLp.js index 36f6736..399d416 100644 --- a/assets/papers_2024_bloom.md.DFgYCwvg.js +++ b/assets/papers_2024_bloom.md.BKiXUzLp.js @@ -1 +1 @@ -import{_ as a,c as t,o as n,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market","description":"","frontmatter":{"layout":"paper","title":"Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market","date":"2024-01-01","authors":["Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/vead089","link":"https://academic.oup.com/ve/article/10/1/vead089/7504441","image":"/assets/papers/2024_bloom.jpg","keywords":["SARS-CoV-2"]},"headers":[],"relativePath":"papers/2024_bloom.md","filePath":"papers/2024_bloom.md"}'),s={name:"papers/2024_bloom.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"In March 2023, the Chinese CDC publicly released raw metagenomic sequencing data for environmental samples collected in early 2020 from the Huanan Seafood Market. Prior to that data release, some scientists had suggested that these samples could be informative for establishing if animals such as raccoon dogs had been infected with severe acute respiratory syndrome virus 2 (SARS-CoV-2). However, no one had analyzed how much SARS-CoV-2 was actually present in the metagenomic sequencing data. After the raw data became available, I fully analyzed the abundance of both viral and animal genetic material in the samples. That analysis, which was published in Virus Evolution, found that the SARS-CoV-2 content of most samples was very low and that the abundance of SARS-CoV-2 was most strongly associated with animals such as largemouth bass that are not plausible candidates for having been infected. Based on these results, I concluded that the metagenomic content of the samples was not informative for determining if any non-human animals in the market had been infected with SARS-CoV-2. One of the authors of an earlier study of these samples, Florence Débarre, recently submitted a response to my paper. Here, I reply in turn to explain why it is important to quantify the abundance of viral material before drawing conclusions from metagenomic sequencing. I also report new analyses of other animal coronaviruses in the samples and show that material from some other animal coronaviruses is much more abundant than SARS-CoV-2 in samples collected on the date when most wildlife stall sampling was performed. I further show that material from some of these animal coronaviruses is associated with the animals they probably infect but that no such association exists for SARS-CoV-2. Overall, these new analyses further emphasize the importance of quantifying the actual amount of viral material in metagenomic samples and underscore why the environmental samples from the Huanan Seafood Market are not informative for determining if any non-human animals were infected with SARS-CoV-2.",-1),l=[r,i];function m(h,c,d,f,u,p){return n(),t("div",null,l)}const v=a(s,[["render",m]]);export{g as __pageData,v as default}; +import{_ as a,c as t,o as n,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market","description":"","frontmatter":{"layout":"paper","title":"Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market","date":"2024-01-01","authors":["Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/vead089","link":"https://academic.oup.com/ve/article/10/1/vead089/7504441","image":"/assets/papers/2024_bloom.jpg","keywords":["SARS-CoV-2"]},"headers":[],"relativePath":"papers/2024_bloom.md","filePath":"papers/2024_bloom.md"}'),s={name:"papers/2024_bloom.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"In March 2023, the Chinese CDC publicly released raw metagenomic sequencing data for environmental samples collected in early 2020 from the Huanan Seafood Market. Prior to that data release, some scientists had suggested that these samples could be informative for establishing if animals such as raccoon dogs had been infected with severe acute respiratory syndrome virus 2 (SARS-CoV-2). However, no one had analyzed how much SARS-CoV-2 was actually present in the metagenomic sequencing data. After the raw data became available, I fully analyzed the abundance of both viral and animal genetic material in the samples. That analysis, which was published in Virus Evolution, found that the SARS-CoV-2 content of most samples was very low and that the abundance of SARS-CoV-2 was most strongly associated with animals such as largemouth bass that are not plausible candidates for having been infected. Based on these results, I concluded that the metagenomic content of the samples was not informative for determining if any non-human animals in the market had been infected with SARS-CoV-2. One of the authors of an earlier study of these samples, Florence Débarre, recently submitted a response to my paper. Here, I reply in turn to explain why it is important to quantify the abundance of viral material before drawing conclusions from metagenomic sequencing. I also report new analyses of other animal coronaviruses in the samples and show that material from some other animal coronaviruses is much more abundant than SARS-CoV-2 in samples collected on the date when most wildlife stall sampling was performed. I further show that material from some of these animal coronaviruses is associated with the animals they probably infect but that no such association exists for SARS-CoV-2. Overall, these new analyses further emphasize the importance of quantifying the actual amount of viral material in metagenomic samples and underscore why the environmental samples from the Huanan Seafood Market are not informative for determining if any non-human animals were infected with SARS-CoV-2.",-1),l=[r,i];function m(h,c,d,f,u,p){return n(),t("div",null,l)}const v=a(s,[["render",m]]);export{g as __pageData,v as default}; diff --git a/assets/papers_2024_bloom.md.DFgYCwvg.lean.js b/assets/papers_2024_bloom.md.BKiXUzLp.lean.js similarity index 97% rename from assets/papers_2024_bloom.md.DFgYCwvg.lean.js rename to assets/papers_2024_bloom.md.BKiXUzLp.lean.js index 36f6736..399d416 100644 --- a/assets/papers_2024_bloom.md.DFgYCwvg.lean.js +++ b/assets/papers_2024_bloom.md.BKiXUzLp.lean.js @@ -1 +1 @@ -import{_ as a,c as t,o as n,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market","description":"","frontmatter":{"layout":"paper","title":"Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market","date":"2024-01-01","authors":["Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/vead089","link":"https://academic.oup.com/ve/article/10/1/vead089/7504441","image":"/assets/papers/2024_bloom.jpg","keywords":["SARS-CoV-2"]},"headers":[],"relativePath":"papers/2024_bloom.md","filePath":"papers/2024_bloom.md"}'),s={name:"papers/2024_bloom.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"In March 2023, the Chinese CDC publicly released raw metagenomic sequencing data for environmental samples collected in early 2020 from the Huanan Seafood Market. Prior to that data release, some scientists had suggested that these samples could be informative for establishing if animals such as raccoon dogs had been infected with severe acute respiratory syndrome virus 2 (SARS-CoV-2). However, no one had analyzed how much SARS-CoV-2 was actually present in the metagenomic sequencing data. After the raw data became available, I fully analyzed the abundance of both viral and animal genetic material in the samples. That analysis, which was published in Virus Evolution, found that the SARS-CoV-2 content of most samples was very low and that the abundance of SARS-CoV-2 was most strongly associated with animals such as largemouth bass that are not plausible candidates for having been infected. Based on these results, I concluded that the metagenomic content of the samples was not informative for determining if any non-human animals in the market had been infected with SARS-CoV-2. One of the authors of an earlier study of these samples, Florence Débarre, recently submitted a response to my paper. Here, I reply in turn to explain why it is important to quantify the abundance of viral material before drawing conclusions from metagenomic sequencing. I also report new analyses of other animal coronaviruses in the samples and show that material from some other animal coronaviruses is much more abundant than SARS-CoV-2 in samples collected on the date when most wildlife stall sampling was performed. I further show that material from some of these animal coronaviruses is associated with the animals they probably infect but that no such association exists for SARS-CoV-2. Overall, these new analyses further emphasize the importance of quantifying the actual amount of viral material in metagenomic samples and underscore why the environmental samples from the Huanan Seafood Market are not informative for determining if any non-human animals were infected with SARS-CoV-2.",-1),l=[r,i];function m(h,c,d,f,u,p){return n(),t("div",null,l)}const v=a(s,[["render",m]]);export{g as __pageData,v as default}; +import{_ as a,c as t,o as n,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market","description":"","frontmatter":{"layout":"paper","title":"Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market","date":"2024-01-01","authors":["Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/vead089","link":"https://academic.oup.com/ve/article/10/1/vead089/7504441","image":"/assets/papers/2024_bloom.jpg","keywords":["SARS-CoV-2"]},"headers":[],"relativePath":"papers/2024_bloom.md","filePath":"papers/2024_bloom.md"}'),s={name:"papers/2024_bloom.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"In March 2023, the Chinese CDC publicly released raw metagenomic sequencing data for environmental samples collected in early 2020 from the Huanan Seafood Market. Prior to that data release, some scientists had suggested that these samples could be informative for establishing if animals such as raccoon dogs had been infected with severe acute respiratory syndrome virus 2 (SARS-CoV-2). However, no one had analyzed how much SARS-CoV-2 was actually present in the metagenomic sequencing data. After the raw data became available, I fully analyzed the abundance of both viral and animal genetic material in the samples. That analysis, which was published in Virus Evolution, found that the SARS-CoV-2 content of most samples was very low and that the abundance of SARS-CoV-2 was most strongly associated with animals such as largemouth bass that are not plausible candidates for having been infected. Based on these results, I concluded that the metagenomic content of the samples was not informative for determining if any non-human animals in the market had been infected with SARS-CoV-2. One of the authors of an earlier study of these samples, Florence Débarre, recently submitted a response to my paper. Here, I reply in turn to explain why it is important to quantify the abundance of viral material before drawing conclusions from metagenomic sequencing. I also report new analyses of other animal coronaviruses in the samples and show that material from some other animal coronaviruses is much more abundant than SARS-CoV-2 in samples collected on the date when most wildlife stall sampling was performed. I further show that material from some of these animal coronaviruses is associated with the animals they probably infect but that no such association exists for SARS-CoV-2. Overall, these new analyses further emphasize the importance of quantifying the actual amount of viral material in metagenomic samples and underscore why the environmental samples from the Huanan Seafood Market are not informative for determining if any non-human animals were infected with SARS-CoV-2.",-1),l=[r,i];function m(h,c,d,f,u,p){return n(),t("div",null,l)}const v=a(s,[["render",m]]);export{g as __pageData,v as default}; diff --git a/assets/papers_2024_carr.md.CVV1gPLS.js b/assets/papers_2024_carr.md.OihxBD-v.js similarity index 95% rename from assets/papers_2024_carr.md.CVV1gPLS.js rename to assets/papers_2024_carr.md.OihxBD-v.js index 2dfd97d..8aff215 100644 --- a/assets/papers_2024_carr.md.CVV1gPLS.js +++ b/assets/papers_2024_carr.md.OihxBD-v.js @@ -1 +1 @@ -import{_ as a,c as e,o as t,g as i}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex","date":"2024-07-15","authors":["Caleb R Carr*","Katharine HD Crawford*","Michael Murphy","Jared G Galloway","Hugh K Haddox","Frederick A Matsen","Kristian G Andersen","Neil P King","Jesse D Bloom"],"journal":"Immunity","doi":"10.1016/j.immuni.2024.06.013","link":"https://www.cell.com/immunity/fulltext/S1074-7613(24)00319-4","image":"/assets/papers/2024_carr.jpg","selected":true,"keywords":["Lassa","Deep mutational scanning","Pseudovirus"]},"headers":[],"relativePath":"papers/2024_carr.md","filePath":"papers/2024_carr.md"}'),s={name:"papers/2024_carr.md"},o=i('

Abstract ​

Lassa virus is estimated to cause thousands of human deaths per year, primarily due to spillovers from its natural host, Mastomys rodents. Efforts to create vaccines and antibody therapeutics must account for the evolutionary variability of Lassa virus’s glycoprotein complex (GPC), which mediates viral entry into cells and is the target of neutralizing antibodies. To map the evolutionary space accessible to GPC, we use pseudovirus deep mutational scanning to measure how nearly all GPC amino-acid mutations affect cell entry and antibody neutralization. Our experiments define functional constraints throughout GPC. We quantify how GPC mutations affect neutralization by a panel of monoclonal antibodies and show that all antibodies are escaped by mutations that exist among natural Lassa virus lineages. Overall, our work describes a biosafety-level-2 method to elucidate the mutational space accessible to GPC and shows how prospective characterization of antigenic variation could aid design of therapeutics and vaccines.

Interactive visualizations ​

The results described in this paper can be interactively visualized at https://dms-vep.org/LASV_Josiah_GP_DMS/

',4),n=[o];function r(c,l,u,d,p,h){return t(),e("div",null,n)}const f=a(s,[["render",r]]);export{_ as __pageData,f as default}; +import{_ as a,c as e,o as t,g as i}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex","date":"2024-07-15","authors":["Caleb R Carr*","Katharine HD Crawford*","Michael Murphy","Jared G Galloway","Hugh K Haddox","Frederick A Matsen","Kristian G Andersen","Neil P King","Jesse D Bloom"],"journal":"Immunity","doi":"10.1016/j.immuni.2024.06.013","link":"https://www.cell.com/immunity/fulltext/S1074-7613(24)00319-4","image":"/assets/papers/2024_carr.jpg","selected":true,"keywords":["Lassa","Deep mutational scanning","Pseudovirus"]},"headers":[],"relativePath":"papers/2024_carr.md","filePath":"papers/2024_carr.md"}'),s={name:"papers/2024_carr.md"},o=i('

Abstract ​

Lassa virus is estimated to cause thousands of human deaths per year, primarily due to spillovers from its natural host, Mastomys rodents. Efforts to create vaccines and antibody therapeutics must account for the evolutionary variability of Lassa virus’s glycoprotein complex (GPC), which mediates viral entry into cells and is the target of neutralizing antibodies. To map the evolutionary space accessible to GPC, we use pseudovirus deep mutational scanning to measure how nearly all GPC amino-acid mutations affect cell entry and antibody neutralization. Our experiments define functional constraints throughout GPC. We quantify how GPC mutations affect neutralization by a panel of monoclonal antibodies and show that all antibodies are escaped by mutations that exist among natural Lassa virus lineages. Overall, our work describes a biosafety-level-2 method to elucidate the mutational space accessible to GPC and shows how prospective characterization of antigenic variation could aid design of therapeutics and vaccines.

Interactive visualizations ​

The results described in this paper can be interactively visualized at https://dms-vep.org/LASV_Josiah_GP_DMS/

',4),n=[o];function r(c,l,u,d,p,h){return t(),e("div",null,n)}const f=a(s,[["render",r]]);export{_ as __pageData,f as default}; diff --git a/assets/papers_2024_carr.md.CVV1gPLS.lean.js b/assets/papers_2024_carr.md.OihxBD-v.lean.js similarity index 88% rename from assets/papers_2024_carr.md.CVV1gPLS.lean.js rename to assets/papers_2024_carr.md.OihxBD-v.lean.js index 7c2295d..ce386b7 100644 --- a/assets/papers_2024_carr.md.CVV1gPLS.lean.js +++ b/assets/papers_2024_carr.md.OihxBD-v.lean.js @@ -1 +1 @@ -import{_ as a,c as e,o as t,g as i}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex","date":"2024-07-15","authors":["Caleb R Carr*","Katharine HD Crawford*","Michael Murphy","Jared G Galloway","Hugh K Haddox","Frederick A Matsen","Kristian G Andersen","Neil P King","Jesse D Bloom"],"journal":"Immunity","doi":"10.1016/j.immuni.2024.06.013","link":"https://www.cell.com/immunity/fulltext/S1074-7613(24)00319-4","image":"/assets/papers/2024_carr.jpg","selected":true,"keywords":["Lassa","Deep mutational scanning","Pseudovirus"]},"headers":[],"relativePath":"papers/2024_carr.md","filePath":"papers/2024_carr.md"}'),s={name:"papers/2024_carr.md"},o=i("",4),n=[o];function r(c,l,u,d,p,h){return t(),e("div",null,n)}const f=a(s,[["render",r]]);export{_ as __pageData,f as default}; +import{_ as a,c as e,o as t,g as i}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex","date":"2024-07-15","authors":["Caleb R Carr*","Katharine HD Crawford*","Michael Murphy","Jared G Galloway","Hugh K Haddox","Frederick A Matsen","Kristian G Andersen","Neil P King","Jesse D Bloom"],"journal":"Immunity","doi":"10.1016/j.immuni.2024.06.013","link":"https://www.cell.com/immunity/fulltext/S1074-7613(24)00319-4","image":"/assets/papers/2024_carr.jpg","selected":true,"keywords":["Lassa","Deep mutational scanning","Pseudovirus"]},"headers":[],"relativePath":"papers/2024_carr.md","filePath":"papers/2024_carr.md"}'),s={name:"papers/2024_carr.md"},o=i("",4),n=[o];function r(c,l,u,d,p,h){return t(),e("div",null,n)}const f=a(s,[["render",r]]);export{_ as __pageData,f as default}; diff --git a/assets/papers_2024_dadonaite_a.md.Npt5bxc1.js b/assets/papers_2024_dadonaite_a.md.BJ4gMuJx.js similarity index 97% rename from assets/papers_2024_dadonaite_a.md.Npt5bxc1.js rename to assets/papers_2024_dadonaite_a.md.BJ4gMuJx.js index aa64033..8ddd2fb 100644 --- a/assets/papers_2024_dadonaite_a.md.Npt5bxc1.js +++ b/assets/papers_2024_dadonaite_a.md.BJ4gMuJx.js @@ -1 +1 @@ -import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades","description":"","frontmatter":{"layout":"paper","title":"Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades","date":"2024-07-03","authors":["Bernadeta Dadonaite","Jack Brown","Teagan E McMahon","Ariana G Farrell","Marlin D Figgins","Daniel Asarnow","Cameron Stewart","Jimin Lee","Jenni Logue","Trevor Bedford","Ben Murrell","Helen Y Chu","David Veesler","Jesse D Bloom"],"journal":"Nature","doi":"10.1038/s41586-024-07636-1","link":"https://www.nature.com/articles/s41586-024-07636-1","image":"/assets/papers/2024_dadonaite_a.jpg","selected":true,"keywords":["SARS-CoV-2","Deep mutational scanning","Pseudovirus"]},"headers":[],"relativePath":"papers/2024_dadonaite_a.md","filePath":"papers/2024_dadonaite_a.md"}'),s={name:"papers/2024_dadonaite_a.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"SARS-CoV-2 variants acquire mutations in spike that promote immune evasion and impact other properties that contribute to viral fitness such as ACE2 receptor binding and cell entry. Knowledge of how mutations affect these spike phenotypes can provide insight into the current and potential future evolution of the virus. Here we use pseudovirus deep mutational scanning to measure how >9,000 mutations across the full XBB.1.5 and BA.2 spikes affect ACE2 binding, cell entry, or escape from human sera. We find that mutations outside the receptor-binding domain (RBD) have meaningfully impacted ACE2 binding during SARS-CoV-2 evolution. We also measure how mutations to the XBB.1.5 spike affect neutralization by serum from individuals who recently had SARS-CoV-2 infections. The strongest serum escape mutations are in the RBD at sites 357, 420, 440, 456, and 473—however, the antigenic impacts of these mutations vary across individuals. We also identify strong escape mutations outside the RBD; however many of them decrease ACE2 binding, suggesting they act by modulating RBD conformation. Notably, the growth rates of human SARS-CoV-2 clades can be explained in substantial part by the measured effects of mutations on spike phenotypes, suggesting our data could enable better prediction of viral evolution.",-1),d=[i,r];function c(l,u,p,h,m,f){return n(),a("div",null,d)}const v=t(s,[["render",c]]);export{_ as __pageData,v as default}; +import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades","description":"","frontmatter":{"layout":"paper","title":"Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades","date":"2024-07-03","authors":["Bernadeta Dadonaite","Jack Brown","Teagan E McMahon","Ariana G Farrell","Marlin D Figgins","Daniel Asarnow","Cameron Stewart","Jimin Lee","Jenni Logue","Trevor Bedford","Ben Murrell","Helen Y Chu","David Veesler","Jesse D Bloom"],"journal":"Nature","doi":"10.1038/s41586-024-07636-1","link":"https://www.nature.com/articles/s41586-024-07636-1","image":"/assets/papers/2024_dadonaite_a.jpg","selected":true,"keywords":["SARS-CoV-2","Deep mutational scanning","Pseudovirus"]},"headers":[],"relativePath":"papers/2024_dadonaite_a.md","filePath":"papers/2024_dadonaite_a.md"}'),s={name:"papers/2024_dadonaite_a.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"SARS-CoV-2 variants acquire mutations in spike that promote immune evasion and impact other properties that contribute to viral fitness such as ACE2 receptor binding and cell entry. Knowledge of how mutations affect these spike phenotypes can provide insight into the current and potential future evolution of the virus. Here we use pseudovirus deep mutational scanning to measure how >9,000 mutations across the full XBB.1.5 and BA.2 spikes affect ACE2 binding, cell entry, or escape from human sera. We find that mutations outside the receptor-binding domain (RBD) have meaningfully impacted ACE2 binding during SARS-CoV-2 evolution. We also measure how mutations to the XBB.1.5 spike affect neutralization by serum from individuals who recently had SARS-CoV-2 infections. The strongest serum escape mutations are in the RBD at sites 357, 420, 440, 456, and 473—however, the antigenic impacts of these mutations vary across individuals. We also identify strong escape mutations outside the RBD; however many of them decrease ACE2 binding, suggesting they act by modulating RBD conformation. Notably, the growth rates of human SARS-CoV-2 clades can be explained in substantial part by the measured effects of mutations on spike phenotypes, suggesting our data could enable better prediction of viral evolution.",-1),d=[i,r];function c(l,u,p,h,m,f){return n(),a("div",null,d)}const v=t(s,[["render",c]]);export{_ as __pageData,v as default}; diff --git a/assets/papers_2024_dadonaite_a.md.Npt5bxc1.lean.js b/assets/papers_2024_dadonaite_a.md.BJ4gMuJx.lean.js similarity index 97% rename from assets/papers_2024_dadonaite_a.md.Npt5bxc1.lean.js rename to assets/papers_2024_dadonaite_a.md.BJ4gMuJx.lean.js index aa64033..8ddd2fb 100644 --- a/assets/papers_2024_dadonaite_a.md.Npt5bxc1.lean.js +++ b/assets/papers_2024_dadonaite_a.md.BJ4gMuJx.lean.js @@ -1 +1 @@ -import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades","description":"","frontmatter":{"layout":"paper","title":"Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades","date":"2024-07-03","authors":["Bernadeta Dadonaite","Jack Brown","Teagan E McMahon","Ariana G Farrell","Marlin D Figgins","Daniel Asarnow","Cameron Stewart","Jimin Lee","Jenni Logue","Trevor Bedford","Ben Murrell","Helen Y Chu","David Veesler","Jesse D Bloom"],"journal":"Nature","doi":"10.1038/s41586-024-07636-1","link":"https://www.nature.com/articles/s41586-024-07636-1","image":"/assets/papers/2024_dadonaite_a.jpg","selected":true,"keywords":["SARS-CoV-2","Deep mutational scanning","Pseudovirus"]},"headers":[],"relativePath":"papers/2024_dadonaite_a.md","filePath":"papers/2024_dadonaite_a.md"}'),s={name:"papers/2024_dadonaite_a.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"SARS-CoV-2 variants acquire mutations in spike that promote immune evasion and impact other properties that contribute to viral fitness such as ACE2 receptor binding and cell entry. Knowledge of how mutations affect these spike phenotypes can provide insight into the current and potential future evolution of the virus. Here we use pseudovirus deep mutational scanning to measure how >9,000 mutations across the full XBB.1.5 and BA.2 spikes affect ACE2 binding, cell entry, or escape from human sera. We find that mutations outside the receptor-binding domain (RBD) have meaningfully impacted ACE2 binding during SARS-CoV-2 evolution. We also measure how mutations to the XBB.1.5 spike affect neutralization by serum from individuals who recently had SARS-CoV-2 infections. The strongest serum escape mutations are in the RBD at sites 357, 420, 440, 456, and 473—however, the antigenic impacts of these mutations vary across individuals. We also identify strong escape mutations outside the RBD; however many of them decrease ACE2 binding, suggesting they act by modulating RBD conformation. Notably, the growth rates of human SARS-CoV-2 clades can be explained in substantial part by the measured effects of mutations on spike phenotypes, suggesting our data could enable better prediction of viral evolution.",-1),d=[i,r];function c(l,u,p,h,m,f){return n(),a("div",null,d)}const v=t(s,[["render",c]]);export{_ as __pageData,v as default}; +import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades","description":"","frontmatter":{"layout":"paper","title":"Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades","date":"2024-07-03","authors":["Bernadeta Dadonaite","Jack Brown","Teagan E McMahon","Ariana G Farrell","Marlin D Figgins","Daniel Asarnow","Cameron Stewart","Jimin Lee","Jenni Logue","Trevor Bedford","Ben Murrell","Helen Y Chu","David Veesler","Jesse D Bloom"],"journal":"Nature","doi":"10.1038/s41586-024-07636-1","link":"https://www.nature.com/articles/s41586-024-07636-1","image":"/assets/papers/2024_dadonaite_a.jpg","selected":true,"keywords":["SARS-CoV-2","Deep mutational scanning","Pseudovirus"]},"headers":[],"relativePath":"papers/2024_dadonaite_a.md","filePath":"papers/2024_dadonaite_a.md"}'),s={name:"papers/2024_dadonaite_a.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"SARS-CoV-2 variants acquire mutations in spike that promote immune evasion and impact other properties that contribute to viral fitness such as ACE2 receptor binding and cell entry. Knowledge of how mutations affect these spike phenotypes can provide insight into the current and potential future evolution of the virus. Here we use pseudovirus deep mutational scanning to measure how >9,000 mutations across the full XBB.1.5 and BA.2 spikes affect ACE2 binding, cell entry, or escape from human sera. We find that mutations outside the receptor-binding domain (RBD) have meaningfully impacted ACE2 binding during SARS-CoV-2 evolution. We also measure how mutations to the XBB.1.5 spike affect neutralization by serum from individuals who recently had SARS-CoV-2 infections. The strongest serum escape mutations are in the RBD at sites 357, 420, 440, 456, and 473—however, the antigenic impacts of these mutations vary across individuals. We also identify strong escape mutations outside the RBD; however many of them decrease ACE2 binding, suggesting they act by modulating RBD conformation. Notably, the growth rates of human SARS-CoV-2 clades can be explained in substantial part by the measured effects of mutations on spike phenotypes, suggesting our data could enable better prediction of viral evolution.",-1),d=[i,r];function c(l,u,p,h,m,f){return n(),a("div",null,d)}const v=t(s,[["render",c]]);export{_ as __pageData,v as default}; diff --git a/assets/papers_2024_dadonaite_b.md.ByEc0Oh_.js b/assets/papers_2024_dadonaite_b.md.CzgcmbCI.js similarity index 95% rename from assets/papers_2024_dadonaite_b.md.ByEc0Oh_.js rename to assets/papers_2024_dadonaite_b.md.CzgcmbCI.js index 96a5dcb..7570cc8 100644 --- a/assets/papers_2024_dadonaite_b.md.ByEc0Oh_.js +++ b/assets/papers_2024_dadonaite_b.md.CzgcmbCI.js @@ -1 +1 @@ -import{_ as e,c as a,o as t,g as i}from"./chunks/framework.BqSDeblO.js";const f=JSON.parse('{"title":"Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance","date":"2024-05-23","authors":["Bernadeta Dadonaite","Jenny J Ahn","Jordan T Ort","Jin Yu","Colleen Furey","Annie Dosey","William W Hannon","Amy Vincent Baker","Richard J Webby","Neil P King","Yan Liu","Scott E Hensley","Thomas P Peacock","Louise H Moncla","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.05.23.595634","link":"https://doi.org/10.1101/2024.05.23.595634","image":"/assets/papers/2024_dadonaite_b.png","selected":true,"keywords":["Influenza","Deep mutational scanning","Pseudovirus"]},"headers":[],"relativePath":"papers/2024_dadonaite_b.md","filePath":"papers/2024_dadonaite_b.md"}'),n={name:"papers/2024_dadonaite_b.md"},s=i('

Abstract ​

H5 influenza is considered a potential pandemic threat. Recently, H5 viruses belonging to clade 2.3.4.4b have caused large outbreaks in avian and multiple non-human mammalian species. Previous studies have identified molecular phenotypes of the viral hemagglutinin (HA) protein that contribute to pandemic potential in humans, including cell entry, receptor preference, HA stability, and reduced neutralization by polyclonal sera. However, prior experimental work has only measured how these phenotypes are affected by a handful of the >10,000 different possible amino-acid mutations to HA. Here we use pseudovirus deep mutational scanning to measure how all mutations to a 2.3.4.4b H5 HA affect each phenotype. We identify mutations that allow HA to better bind α2-6-linked sialic acids, and show that some viruses already carry mutations that stabilize HA. We also measure how all HA mutations affect neutralization by sera from mice and ferrets vaccinated against or infected with 2.3.4.4b H5 viruses. These antigenic maps enable rapid assessment of when new viral strains have acquired mutations that may create mismatches with candidate vaccine strains. Overall, the systematic nature of deep mutational scanning combined with the safety of pseudoviruses enables comprehensive measurements of the phenotypic effects of mutations that can inform real-time interpretation of viral variation observed during surveillance of H5 influenza.

Interactive visualizations ​

The results described in this paper can be interactively visualized at https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/

',4),o=[s];function r(l,c,d,u,h,m){return t(),a("div",null,o)}const _=e(n,[["render",r]]);export{f as __pageData,_ as default}; +import{_ as e,c as a,o as t,g as i}from"./chunks/framework.D4bY2S_W.js";const f=JSON.parse('{"title":"Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance","date":"2024-05-23","authors":["Bernadeta Dadonaite","Jenny J Ahn","Jordan T Ort","Jin Yu","Colleen Furey","Annie Dosey","William W Hannon","Amy Vincent Baker","Richard J Webby","Neil P King","Yan Liu","Scott E Hensley","Thomas P Peacock","Louise H Moncla","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.05.23.595634","link":"https://doi.org/10.1101/2024.05.23.595634","image":"/assets/papers/2024_dadonaite_b.png","selected":true,"keywords":["Influenza","Deep mutational scanning","Pseudovirus"]},"headers":[],"relativePath":"papers/2024_dadonaite_b.md","filePath":"papers/2024_dadonaite_b.md"}'),n={name:"papers/2024_dadonaite_b.md"},s=i('

Abstract ​

H5 influenza is considered a potential pandemic threat. Recently, H5 viruses belonging to clade 2.3.4.4b have caused large outbreaks in avian and multiple non-human mammalian species. Previous studies have identified molecular phenotypes of the viral hemagglutinin (HA) protein that contribute to pandemic potential in humans, including cell entry, receptor preference, HA stability, and reduced neutralization by polyclonal sera. However, prior experimental work has only measured how these phenotypes are affected by a handful of the >10,000 different possible amino-acid mutations to HA. Here we use pseudovirus deep mutational scanning to measure how all mutations to a 2.3.4.4b H5 HA affect each phenotype. We identify mutations that allow HA to better bind α2-6-linked sialic acids, and show that some viruses already carry mutations that stabilize HA. We also measure how all HA mutations affect neutralization by sera from mice and ferrets vaccinated against or infected with 2.3.4.4b H5 viruses. These antigenic maps enable rapid assessment of when new viral strains have acquired mutations that may create mismatches with candidate vaccine strains. Overall, the systematic nature of deep mutational scanning combined with the safety of pseudoviruses enables comprehensive measurements of the phenotypic effects of mutations that can inform real-time interpretation of viral variation observed during surveillance of H5 influenza.

Interactive visualizations ​

The results described in this paper can be interactively visualized at https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/

',4),o=[s];function r(l,c,d,u,h,m){return t(),a("div",null,o)}const _=e(n,[["render",r]]);export{f as __pageData,_ as default}; diff --git a/assets/papers_2024_dadonaite_b.md.ByEc0Oh_.lean.js b/assets/papers_2024_dadonaite_b.md.CzgcmbCI.lean.js similarity index 88% rename from assets/papers_2024_dadonaite_b.md.ByEc0Oh_.lean.js rename to assets/papers_2024_dadonaite_b.md.CzgcmbCI.lean.js index 5f185b0..1be9dd1 100644 --- a/assets/papers_2024_dadonaite_b.md.ByEc0Oh_.lean.js +++ b/assets/papers_2024_dadonaite_b.md.CzgcmbCI.lean.js @@ -1 +1 @@ -import{_ as e,c as a,o as t,g as i}from"./chunks/framework.BqSDeblO.js";const f=JSON.parse('{"title":"Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance","date":"2024-05-23","authors":["Bernadeta Dadonaite","Jenny J Ahn","Jordan T Ort","Jin Yu","Colleen Furey","Annie Dosey","William W Hannon","Amy Vincent Baker","Richard J Webby","Neil P King","Yan Liu","Scott E Hensley","Thomas P Peacock","Louise H Moncla","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.05.23.595634","link":"https://doi.org/10.1101/2024.05.23.595634","image":"/assets/papers/2024_dadonaite_b.png","selected":true,"keywords":["Influenza","Deep mutational scanning","Pseudovirus"]},"headers":[],"relativePath":"papers/2024_dadonaite_b.md","filePath":"papers/2024_dadonaite_b.md"}'),n={name:"papers/2024_dadonaite_b.md"},s=i("",4),o=[s];function r(l,c,d,u,h,m){return t(),a("div",null,o)}const _=e(n,[["render",r]]);export{f as __pageData,_ as default}; +import{_ as e,c as a,o as t,g as i}from"./chunks/framework.D4bY2S_W.js";const f=JSON.parse('{"title":"Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance","date":"2024-05-23","authors":["Bernadeta Dadonaite","Jenny J Ahn","Jordan T Ort","Jin Yu","Colleen Furey","Annie Dosey","William W Hannon","Amy Vincent Baker","Richard J Webby","Neil P King","Yan Liu","Scott E Hensley","Thomas P Peacock","Louise H Moncla","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.05.23.595634","link":"https://doi.org/10.1101/2024.05.23.595634","image":"/assets/papers/2024_dadonaite_b.png","selected":true,"keywords":["Influenza","Deep mutational scanning","Pseudovirus"]},"headers":[],"relativePath":"papers/2024_dadonaite_b.md","filePath":"papers/2024_dadonaite_b.md"}'),n={name:"papers/2024_dadonaite_b.md"},s=i("",4),o=[s];function r(l,c,d,u,h,m){return t(),a("div",null,o)}const _=e(n,[["render",r]]);export{f as __pageData,_ as default}; diff --git a/assets/papers_2024_hannon.md.LNbwYpi-.js b/assets/papers_2024_hannon.md.Dd9QC8Cw.js similarity index 97% rename from assets/papers_2024_hannon.md.LNbwYpi-.js rename to assets/papers_2024_hannon.md.Dd9QC8Cw.js index e1e0441..db28d49 100644 --- a/assets/papers_2024_hannon.md.LNbwYpi-.js +++ b/assets/papers_2024_hannon.md.Dd9QC8Cw.js @@ -1 +1 @@ -import{_ as a,c as o,o as n,b as e,d as t}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets","description":"","frontmatter":{"layout":"paper","title":"dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets","date":"2024-07-17","authors":["William W Hannon","Jesse D Bloom"],"journal":"Journal of Open Source Software","doi":"10.21105/joss.06129","link":"https://joss.theoj.org/papers/10.21105/joss.06129","image":"/assets/papers/2024_hannon.jpg","keywords":["Software tools","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2024_hannon.md","filePath":"papers/2024_hannon.md"}'),s={name:"papers/2024_hannon.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Understanding how mutations impact a protein’s functions is valuable for many types of biological questions. High-throughput techniques such as deep-mutational scanning (DMS) have greatly expanded the number of mutation-function datasets. For instance, DMS has been used to determine how mutations to viral proteins affect antibody escape (Dadonaite et al. 2023), receptor affinity (Starr et al. 2020), and essential functions such as viral genome transcription and replication (Li et al. 2023). With the growth of sequence databases, in some cases the effects of mutations can also be inferred from phylogenies of natural sequences (Bloom and Neher 2023) (Figure 1).",-1),d=e("p",null,[t("The mutation-based data generated by these approaches is often best understood in the context of a protein’s 3D structure; for instance, to assess questions like how mutations that affect antibody escape relate to the physical antibody binding epitope on the protein. However, current approaches for visualizing mutation data in the context of a protein’s structure are often cumbersome and require multiple steps and softwares. To streamline the visualization of mutation-associated data in the context of a protein structure, we developed a web-based tool, dms-viz. With dms-viz, users can straightforwardly visualize mutation-based data such as those from DMS experiments in the context of a 3D protein model in an interactive format. See "),e("a",{href:"https://dms-viz.github.io/",target:"_blank",rel:"noreferrer"},"https://dms-viz.github.io/"),t(" to use dms-viz.")],-1),c=[i,r,d];function u(l,h,p,m,f,b){return n(),o("div",null,c)}const v=a(s,[["render",u]]);export{g as __pageData,v as default}; +import{_ as a,c as o,o as n,b as e,d as t}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets","description":"","frontmatter":{"layout":"paper","title":"dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets","date":"2024-07-17","authors":["William W Hannon","Jesse D Bloom"],"journal":"Journal of Open Source Software","doi":"10.21105/joss.06129","link":"https://joss.theoj.org/papers/10.21105/joss.06129","image":"/assets/papers/2024_hannon.jpg","keywords":["Software tools","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2024_hannon.md","filePath":"papers/2024_hannon.md"}'),s={name:"papers/2024_hannon.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Understanding how mutations impact a protein’s functions is valuable for many types of biological questions. High-throughput techniques such as deep-mutational scanning (DMS) have greatly expanded the number of mutation-function datasets. For instance, DMS has been used to determine how mutations to viral proteins affect antibody escape (Dadonaite et al. 2023), receptor affinity (Starr et al. 2020), and essential functions such as viral genome transcription and replication (Li et al. 2023). With the growth of sequence databases, in some cases the effects of mutations can also be inferred from phylogenies of natural sequences (Bloom and Neher 2023) (Figure 1).",-1),d=e("p",null,[t("The mutation-based data generated by these approaches is often best understood in the context of a protein’s 3D structure; for instance, to assess questions like how mutations that affect antibody escape relate to the physical antibody binding epitope on the protein. However, current approaches for visualizing mutation data in the context of a protein’s structure are often cumbersome and require multiple steps and softwares. To streamline the visualization of mutation-associated data in the context of a protein structure, we developed a web-based tool, dms-viz. With dms-viz, users can straightforwardly visualize mutation-based data such as those from DMS experiments in the context of a 3D protein model in an interactive format. See "),e("a",{href:"https://dms-viz.github.io/",target:"_blank",rel:"noreferrer"},"https://dms-viz.github.io/"),t(" to use dms-viz.")],-1),c=[i,r,d];function u(l,h,p,m,f,b){return n(),o("div",null,c)}const v=a(s,[["render",u]]);export{g as __pageData,v as default}; diff --git a/assets/papers_2024_hannon.md.LNbwYpi-.lean.js b/assets/papers_2024_hannon.md.Dd9QC8Cw.lean.js similarity index 97% rename from assets/papers_2024_hannon.md.LNbwYpi-.lean.js rename to assets/papers_2024_hannon.md.Dd9QC8Cw.lean.js index e1e0441..db28d49 100644 --- a/assets/papers_2024_hannon.md.LNbwYpi-.lean.js +++ b/assets/papers_2024_hannon.md.Dd9QC8Cw.lean.js @@ -1 +1 @@ -import{_ as a,c as o,o as n,b as e,d as t}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets","description":"","frontmatter":{"layout":"paper","title":"dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets","date":"2024-07-17","authors":["William W Hannon","Jesse D Bloom"],"journal":"Journal of Open Source Software","doi":"10.21105/joss.06129","link":"https://joss.theoj.org/papers/10.21105/joss.06129","image":"/assets/papers/2024_hannon.jpg","keywords":["Software tools","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2024_hannon.md","filePath":"papers/2024_hannon.md"}'),s={name:"papers/2024_hannon.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Understanding how mutations impact a protein’s functions is valuable for many types of biological questions. High-throughput techniques such as deep-mutational scanning (DMS) have greatly expanded the number of mutation-function datasets. For instance, DMS has been used to determine how mutations to viral proteins affect antibody escape (Dadonaite et al. 2023), receptor affinity (Starr et al. 2020), and essential functions such as viral genome transcription and replication (Li et al. 2023). With the growth of sequence databases, in some cases the effects of mutations can also be inferred from phylogenies of natural sequences (Bloom and Neher 2023) (Figure 1).",-1),d=e("p",null,[t("The mutation-based data generated by these approaches is often best understood in the context of a protein’s 3D structure; for instance, to assess questions like how mutations that affect antibody escape relate to the physical antibody binding epitope on the protein. However, current approaches for visualizing mutation data in the context of a protein’s structure are often cumbersome and require multiple steps and softwares. To streamline the visualization of mutation-associated data in the context of a protein structure, we developed a web-based tool, dms-viz. With dms-viz, users can straightforwardly visualize mutation-based data such as those from DMS experiments in the context of a 3D protein model in an interactive format. See "),e("a",{href:"https://dms-viz.github.io/",target:"_blank",rel:"noreferrer"},"https://dms-viz.github.io/"),t(" to use dms-viz.")],-1),c=[i,r,d];function u(l,h,p,m,f,b){return n(),o("div",null,c)}const v=a(s,[["render",u]]);export{g as __pageData,v as default}; +import{_ as a,c as o,o as n,b as e,d as t}from"./chunks/framework.D4bY2S_W.js";const g=JSON.parse('{"title":"dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets","description":"","frontmatter":{"layout":"paper","title":"dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets","date":"2024-07-17","authors":["William W Hannon","Jesse D Bloom"],"journal":"Journal of Open Source Software","doi":"10.21105/joss.06129","link":"https://joss.theoj.org/papers/10.21105/joss.06129","image":"/assets/papers/2024_hannon.jpg","keywords":["Software tools","Deep mutational scanning"]},"headers":[],"relativePath":"papers/2024_hannon.md","filePath":"papers/2024_hannon.md"}'),s={name:"papers/2024_hannon.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Understanding how mutations impact a protein’s functions is valuable for many types of biological questions. High-throughput techniques such as deep-mutational scanning (DMS) have greatly expanded the number of mutation-function datasets. For instance, DMS has been used to determine how mutations to viral proteins affect antibody escape (Dadonaite et al. 2023), receptor affinity (Starr et al. 2020), and essential functions such as viral genome transcription and replication (Li et al. 2023). With the growth of sequence databases, in some cases the effects of mutations can also be inferred from phylogenies of natural sequences (Bloom and Neher 2023) (Figure 1).",-1),d=e("p",null,[t("The mutation-based data generated by these approaches is often best understood in the context of a protein’s 3D structure; for instance, to assess questions like how mutations that affect antibody escape relate to the physical antibody binding epitope on the protein. However, current approaches for visualizing mutation data in the context of a protein’s structure are often cumbersome and require multiple steps and softwares. To streamline the visualization of mutation-associated data in the context of a protein structure, we developed a web-based tool, dms-viz. With dms-viz, users can straightforwardly visualize mutation-based data such as those from DMS experiments in the context of a 3D protein model in an interactive format. See "),e("a",{href:"https://dms-viz.github.io/",target:"_blank",rel:"noreferrer"},"https://dms-viz.github.io/"),t(" to use dms-viz.")],-1),c=[i,r,d];function u(l,h,p,m,f,b){return n(),o("div",null,c)}const v=a(s,[["render",u]]);export{g as __pageData,v as default}; diff --git a/assets/papers_2024_larsen.md.g-ImRzQ4.js b/assets/papers_2024_larsen.md.CdCk92Pt.js similarity index 94% rename from assets/papers_2024_larsen.md.g-ImRzQ4.js rename to assets/papers_2024_larsen.md.CdCk92Pt.js index 84fe66e..3c3cdc7 100644 --- a/assets/papers_2024_larsen.md.g-ImRzQ4.js +++ b/assets/papers_2024_larsen.md.CdCk92Pt.js @@ -1 +1 @@ -import{_ as a,c as e,o as t,g as i}from"./chunks/framework.BqSDeblO.js";const f=JSON.parse('{"title":"Functional and antigenic landscape of the Nipah virus receptor binding protein","description":"","frontmatter":{"layout":"paper","title":"Functional and antigenic landscape of the Nipah virus receptor binding protein","date":"2024-04-17","authors":["Brendan B Larsen","Teagan McMahon","Jack T Brown","Zhaoqian Wang","Caelan E Radford","James E Crowe","David Veesler","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.04.17.589977","link":"https://www.biorxiv.org/content/10.1101/2024.04.17.589977v1.abstract","image":"/assets/papers/2024_larsen.jpg","keywords":["Nipah","Deep mutational scanning","Pseudovirus"]},"headers":[],"relativePath":"papers/2024_larsen.md","filePath":"papers/2024_larsen.md"}'),n={name:"papers/2024_larsen.md"},r=i('

Abstract ​

Nipah virus recurrently spills over to humans, causing fatal infections. The viral receptor-binding protein (RBP or G) attaches to host receptors and is a major target of neutralizing antibodies. Here we use deep mutational scanning to measure how all amino-acid mutations to the RBP affect cell entry, receptor binding, and escape from neutralizing antibodies. We identify functionally constrained regions of the RBP, including sites involved in oligomerization, along with mutations that differentially modulate RBP binding to its two ephrin receptors. We map escape mutations for six anti-RBP antibodies, and find that few antigenic mutations are present in natural Nipah strains. Our findings offer insights into the potential for functional and antigenic evolution of the RBP that can inform the development of antibody therapies and vaccines.

Interactive visualizations ​

The results described in this paper can be interactively visualized at https://dms-vep.org/Nipah_Malaysia_RBP_DMS/

',4),o=[r];function s(l,c,p,d,h,u){return t(),e("div",null,o)}const m=a(n,[["render",s]]);export{f as __pageData,m as default}; +import{_ as a,c as e,o as t,g as i}from"./chunks/framework.D4bY2S_W.js";const f=JSON.parse('{"title":"Functional and antigenic landscape of the Nipah virus receptor binding protein","description":"","frontmatter":{"layout":"paper","title":"Functional and antigenic landscape of the Nipah virus receptor binding protein","date":"2024-04-17","authors":["Brendan B Larsen","Teagan McMahon","Jack T Brown","Zhaoqian Wang","Caelan E Radford","James E Crowe","David Veesler","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.04.17.589977","link":"https://www.biorxiv.org/content/10.1101/2024.04.17.589977v1.abstract","image":"/assets/papers/2024_larsen.jpg","keywords":["Nipah","Deep mutational scanning","Pseudovirus"]},"headers":[],"relativePath":"papers/2024_larsen.md","filePath":"papers/2024_larsen.md"}'),n={name:"papers/2024_larsen.md"},r=i('

Abstract ​

Nipah virus recurrently spills over to humans, causing fatal infections. The viral receptor-binding protein (RBP or G) attaches to host receptors and is a major target of neutralizing antibodies. Here we use deep mutational scanning to measure how all amino-acid mutations to the RBP affect cell entry, receptor binding, and escape from neutralizing antibodies. We identify functionally constrained regions of the RBP, including sites involved in oligomerization, along with mutations that differentially modulate RBP binding to its two ephrin receptors. We map escape mutations for six anti-RBP antibodies, and find that few antigenic mutations are present in natural Nipah strains. Our findings offer insights into the potential for functional and antigenic evolution of the RBP that can inform the development of antibody therapies and vaccines.

Interactive visualizations ​

The results described in this paper can be interactively visualized at https://dms-vep.org/Nipah_Malaysia_RBP_DMS/

',4),o=[r];function s(l,c,p,d,h,u){return t(),e("div",null,o)}const m=a(n,[["render",s]]);export{f as __pageData,m as default}; diff --git a/assets/papers_2024_larsen.md.g-ImRzQ4.lean.js b/assets/papers_2024_larsen.md.CdCk92Pt.lean.js similarity index 86% rename from assets/papers_2024_larsen.md.g-ImRzQ4.lean.js rename to assets/papers_2024_larsen.md.CdCk92Pt.lean.js index 4dc4345..20711fd 100644 --- a/assets/papers_2024_larsen.md.g-ImRzQ4.lean.js +++ b/assets/papers_2024_larsen.md.CdCk92Pt.lean.js @@ -1 +1 @@ -import{_ as a,c as e,o as t,g as i}from"./chunks/framework.BqSDeblO.js";const f=JSON.parse('{"title":"Functional and antigenic landscape of the Nipah virus receptor binding protein","description":"","frontmatter":{"layout":"paper","title":"Functional and antigenic landscape of the Nipah virus receptor binding protein","date":"2024-04-17","authors":["Brendan B Larsen","Teagan McMahon","Jack T Brown","Zhaoqian Wang","Caelan E Radford","James E Crowe","David Veesler","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.04.17.589977","link":"https://www.biorxiv.org/content/10.1101/2024.04.17.589977v1.abstract","image":"/assets/papers/2024_larsen.jpg","keywords":["Nipah","Deep mutational scanning","Pseudovirus"]},"headers":[],"relativePath":"papers/2024_larsen.md","filePath":"papers/2024_larsen.md"}'),n={name:"papers/2024_larsen.md"},r=i("",4),o=[r];function s(l,c,p,d,h,u){return t(),e("div",null,o)}const m=a(n,[["render",s]]);export{f as __pageData,m as default}; +import{_ as a,c as e,o as t,g as i}from"./chunks/framework.D4bY2S_W.js";const f=JSON.parse('{"title":"Functional and antigenic landscape of the Nipah virus receptor binding protein","description":"","frontmatter":{"layout":"paper","title":"Functional and antigenic landscape of the Nipah virus receptor binding protein","date":"2024-04-17","authors":["Brendan B Larsen","Teagan McMahon","Jack T Brown","Zhaoqian Wang","Caelan E Radford","James E Crowe","David Veesler","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.04.17.589977","link":"https://www.biorxiv.org/content/10.1101/2024.04.17.589977v1.abstract","image":"/assets/papers/2024_larsen.jpg","keywords":["Nipah","Deep mutational scanning","Pseudovirus"]},"headers":[],"relativePath":"papers/2024_larsen.md","filePath":"papers/2024_larsen.md"}'),n={name:"papers/2024_larsen.md"},r=i("",4),o=[r];function s(l,c,p,d,h,u){return t(),e("div",null,o)}const m=a(n,[["render",s]]);export{f as __pageData,m as default}; diff --git a/assets/papers_2024_loes.md.C6ZJlmPc.js b/assets/papers_2024_loes.md.Ctn4IIjR.js similarity index 98% rename from assets/papers_2024_loes.md.C6ZJlmPc.js rename to assets/papers_2024_loes.md.Ctn4IIjR.js index b062ea4..8906b95 100644 --- a/assets/papers_2024_loes.md.C6ZJlmPc.js +++ b/assets/papers_2024_loes.md.Ctn4IIjR.js @@ -1 +1 @@ -import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.BqSDeblO.js";const f=JSON.parse('{"title":"High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains","description":"","frontmatter":{"layout":"paper","title":"High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains","date":"2024-03-08","authors":["Andrea N Loes","Rosario Araceli L Tarabi","John Huddleston","Lisa Touyon","Sook San Wong","Samuel MS Cheng","Nancy HL Leung","William W Hannon","Trevor Bedford","Sarah Cobey","Benjamin J Cowling","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.03.08.584176","link":"https://www.biorxiv.org/content/10.1101/2024.03.08.584176v1.abstract","image":"/assets/papers/2024_loes.jpg","keywords":["Influenza","Immunity"],"selected":true},"headers":[],"relativePath":"papers/2024_loes.md","filePath":"papers/2024_loes.md"}'),s={name:"papers/2024_loes.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,[a("The high genetic diversity of influenza viruses means that traditional serological assays have too low throughput to measure serum antibody neutralization titers against all relevant strains. To overcome this challenge, we have developed a sequencing-based neutralization assay that simultaneously measures titers against many viral strains using small serum volumes via a workflow similar to traditional neutralization assays. The key innovation is to incorporate unique nucleotide barcodes into the hemagglutinin (HA) genomic segment, and then pool viruses with numerous different barcoded HA variants and quantify infectivity of all of them simultaneously using next-generation sequencing. With this approach, a single researcher performed the equivalent of 2,880 traditional neutralization assays (80 serum samples against 36 viral strains) in approximately one month. We applied the sequencing-based assay to quantify the impact of influenza vaccination on neutralization titers against recent human H1N1 strains for individuals who had or had not also received a vaccine in the previous year. We found that the viral strain specificities of the neutralizing antibodies elicited by vaccination vary among individuals, and that vaccination induced a smaller increase in titers for individuals who had also received a vaccine the previous year—although the titers six months after vaccination were similar in individuals with and without the previous-year vaccination. We also identified a subset of individuals with low titers to a subclade of recent H1N1 even after vaccination. This study demonstrates the utility of high-throughput sequencing-based neutralization assays that enable titers to be simultaneously measured against many different viral strains. We provide a detailed experimental protocol (DOI: "),e("a",{href:"https://dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1",target:"_blank",rel:"noreferrer"},"https://dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1"),a(") and a computational pipeline ("),e("a",{href:"https://github.com/jbloomlab/seqneut-pipeline",target:"_blank",rel:"noreferrer"},"https://github.com/jbloomlab/seqneut-pipeline"),a(") for the sequencing-based neutralization assays to facilitate the use of this method by others.")],-1),l=[o,r];function u(d,c,h,p,m,g){return n(),i("div",null,l)}const b=t(s,[["render",u]]);export{f as __pageData,b as default}; +import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.D4bY2S_W.js";const f=JSON.parse('{"title":"High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains","description":"","frontmatter":{"layout":"paper","title":"High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains","date":"2024-03-08","authors":["Andrea N Loes","Rosario Araceli L Tarabi","John Huddleston","Lisa Touyon","Sook San Wong","Samuel MS Cheng","Nancy HL Leung","William W Hannon","Trevor Bedford","Sarah Cobey","Benjamin J Cowling","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.03.08.584176","link":"https://www.biorxiv.org/content/10.1101/2024.03.08.584176v1.abstract","image":"/assets/papers/2024_loes.jpg","keywords":["Influenza","Immunity"],"selected":true},"headers":[],"relativePath":"papers/2024_loes.md","filePath":"papers/2024_loes.md"}'),s={name:"papers/2024_loes.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,[a("The high genetic diversity of influenza viruses means that traditional serological assays have too low throughput to measure serum antibody neutralization titers against all relevant strains. To overcome this challenge, we have developed a sequencing-based neutralization assay that simultaneously measures titers against many viral strains using small serum volumes via a workflow similar to traditional neutralization assays. The key innovation is to incorporate unique nucleotide barcodes into the hemagglutinin (HA) genomic segment, and then pool viruses with numerous different barcoded HA variants and quantify infectivity of all of them simultaneously using next-generation sequencing. With this approach, a single researcher performed the equivalent of 2,880 traditional neutralization assays (80 serum samples against 36 viral strains) in approximately one month. We applied the sequencing-based assay to quantify the impact of influenza vaccination on neutralization titers against recent human H1N1 strains for individuals who had or had not also received a vaccine in the previous year. We found that the viral strain specificities of the neutralizing antibodies elicited by vaccination vary among individuals, and that vaccination induced a smaller increase in titers for individuals who had also received a vaccine the previous year—although the titers six months after vaccination were similar in individuals with and without the previous-year vaccination. We also identified a subset of individuals with low titers to a subclade of recent H1N1 even after vaccination. This study demonstrates the utility of high-throughput sequencing-based neutralization assays that enable titers to be simultaneously measured against many different viral strains. We provide a detailed experimental protocol (DOI: "),e("a",{href:"https://dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1",target:"_blank",rel:"noreferrer"},"https://dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1"),a(") and a computational pipeline ("),e("a",{href:"https://github.com/jbloomlab/seqneut-pipeline",target:"_blank",rel:"noreferrer"},"https://github.com/jbloomlab/seqneut-pipeline"),a(") for the sequencing-based neutralization assays to facilitate the use of this method by others.")],-1),l=[o,r];function u(d,c,h,p,m,g){return n(),i("div",null,l)}const b=t(s,[["render",u]]);export{f as __pageData,b as default}; diff --git a/assets/papers_2024_loes.md.C6ZJlmPc.lean.js b/assets/papers_2024_loes.md.Ctn4IIjR.lean.js similarity index 98% rename from assets/papers_2024_loes.md.C6ZJlmPc.lean.js rename to assets/papers_2024_loes.md.Ctn4IIjR.lean.js index b062ea4..8906b95 100644 --- a/assets/papers_2024_loes.md.C6ZJlmPc.lean.js +++ b/assets/papers_2024_loes.md.Ctn4IIjR.lean.js @@ -1 +1 @@ -import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.BqSDeblO.js";const f=JSON.parse('{"title":"High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains","description":"","frontmatter":{"layout":"paper","title":"High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains","date":"2024-03-08","authors":["Andrea N Loes","Rosario Araceli L Tarabi","John Huddleston","Lisa Touyon","Sook San Wong","Samuel MS Cheng","Nancy HL Leung","William W Hannon","Trevor Bedford","Sarah Cobey","Benjamin J Cowling","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.03.08.584176","link":"https://www.biorxiv.org/content/10.1101/2024.03.08.584176v1.abstract","image":"/assets/papers/2024_loes.jpg","keywords":["Influenza","Immunity"],"selected":true},"headers":[],"relativePath":"papers/2024_loes.md","filePath":"papers/2024_loes.md"}'),s={name:"papers/2024_loes.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,[a("The high genetic diversity of influenza viruses means that traditional serological assays have too low throughput to measure serum antibody neutralization titers against all relevant strains. To overcome this challenge, we have developed a sequencing-based neutralization assay that simultaneously measures titers against many viral strains using small serum volumes via a workflow similar to traditional neutralization assays. The key innovation is to incorporate unique nucleotide barcodes into the hemagglutinin (HA) genomic segment, and then pool viruses with numerous different barcoded HA variants and quantify infectivity of all of them simultaneously using next-generation sequencing. With this approach, a single researcher performed the equivalent of 2,880 traditional neutralization assays (80 serum samples against 36 viral strains) in approximately one month. We applied the sequencing-based assay to quantify the impact of influenza vaccination on neutralization titers against recent human H1N1 strains for individuals who had or had not also received a vaccine in the previous year. We found that the viral strain specificities of the neutralizing antibodies elicited by vaccination vary among individuals, and that vaccination induced a smaller increase in titers for individuals who had also received a vaccine the previous year—although the titers six months after vaccination were similar in individuals with and without the previous-year vaccination. We also identified a subset of individuals with low titers to a subclade of recent H1N1 even after vaccination. This study demonstrates the utility of high-throughput sequencing-based neutralization assays that enable titers to be simultaneously measured against many different viral strains. We provide a detailed experimental protocol (DOI: "),e("a",{href:"https://dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1",target:"_blank",rel:"noreferrer"},"https://dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1"),a(") and a computational pipeline ("),e("a",{href:"https://github.com/jbloomlab/seqneut-pipeline",target:"_blank",rel:"noreferrer"},"https://github.com/jbloomlab/seqneut-pipeline"),a(") for the sequencing-based neutralization assays to facilitate the use of this method by others.")],-1),l=[o,r];function u(d,c,h,p,m,g){return n(),i("div",null,l)}const b=t(s,[["render",u]]);export{f as __pageData,b as default}; +import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.D4bY2S_W.js";const f=JSON.parse('{"title":"High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains","description":"","frontmatter":{"layout":"paper","title":"High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains","date":"2024-03-08","authors":["Andrea N Loes","Rosario Araceli L Tarabi","John Huddleston","Lisa Touyon","Sook San Wong","Samuel MS Cheng","Nancy HL Leung","William W Hannon","Trevor Bedford","Sarah Cobey","Benjamin J Cowling","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.03.08.584176","link":"https://www.biorxiv.org/content/10.1101/2024.03.08.584176v1.abstract","image":"/assets/papers/2024_loes.jpg","keywords":["Influenza","Immunity"],"selected":true},"headers":[],"relativePath":"papers/2024_loes.md","filePath":"papers/2024_loes.md"}'),s={name:"papers/2024_loes.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,[a("The high genetic diversity of influenza viruses means that traditional serological assays have too low throughput to measure serum antibody neutralization titers against all relevant strains. To overcome this challenge, we have developed a sequencing-based neutralization assay that simultaneously measures titers against many viral strains using small serum volumes via a workflow similar to traditional neutralization assays. The key innovation is to incorporate unique nucleotide barcodes into the hemagglutinin (HA) genomic segment, and then pool viruses with numerous different barcoded HA variants and quantify infectivity of all of them simultaneously using next-generation sequencing. With this approach, a single researcher performed the equivalent of 2,880 traditional neutralization assays (80 serum samples against 36 viral strains) in approximately one month. We applied the sequencing-based assay to quantify the impact of influenza vaccination on neutralization titers against recent human H1N1 strains for individuals who had or had not also received a vaccine in the previous year. We found that the viral strain specificities of the neutralizing antibodies elicited by vaccination vary among individuals, and that vaccination induced a smaller increase in titers for individuals who had also received a vaccine the previous year—although the titers six months after vaccination were similar in individuals with and without the previous-year vaccination. We also identified a subset of individuals with low titers to a subclade of recent H1N1 even after vaccination. This study demonstrates the utility of high-throughput sequencing-based neutralization assays that enable titers to be simultaneously measured against many different viral strains. We provide a detailed experimental protocol (DOI: "),e("a",{href:"https://dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1",target:"_blank",rel:"noreferrer"},"https://dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1"),a(") and a computational pipeline ("),e("a",{href:"https://github.com/jbloomlab/seqneut-pipeline",target:"_blank",rel:"noreferrer"},"https://github.com/jbloomlab/seqneut-pipeline"),a(") for the sequencing-based neutralization assays to facilitate the use of this method by others.")],-1),l=[o,r];function u(d,c,h,p,m,g){return n(),i("div",null,l)}const b=t(s,[["render",u]]);export{f as __pageData,b as default}; diff --git a/assets/papers_2024_welsh.md.hpaBpE24.js b/assets/papers_2024_welsh.md.DE5cBDQg.js similarity index 97% rename from assets/papers_2024_welsh.md.hpaBpE24.js rename to assets/papers_2024_welsh.md.DE5cBDQg.js index 00f7686..400b722 100644 --- a/assets/papers_2024_welsh.md.hpaBpE24.js +++ b/assets/papers_2024_welsh.md.DE5cBDQg.js @@ -1 +1 @@ -import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin","date":"2024-07-19","authors":["Frances C Welsh","Rachel T Eguia","Juhye M Lee","Hugh K Haddox","Jared Galloway","Nguyen Van Vinh Chau","Andrea N Loes","John Huddleston","Timothy C Yu","Mai Quynh Le","Nguyen TD Nhat","Nguyen Thi Le Thanh","Alexander L Greninger","Helen Y Chu","Janet A Englund","Trevor Bedford","Frederick A Matsen IV","Maciej F Boni","Jesse D Bloom"],"journal":"Cell Host & Microbe","doi":"10.1016/j.chom.2024.06.015","link":"https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(24)00233-6","image":"/assets/papers/2024_welsh.jpg","keywords":["Influenza","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2024_welsh.md","filePath":"papers/2024_welsh.md"}'),s={name:"papers/2024_welsh.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Human influenza virus evolves to escape neutralization by polyclonal antibodies. However, we have a limited understanding of how the antigenic effects of viral mutations vary across the human population and how this heterogeneity affects virus evolution. Here, we use deep mutational scanning to map how mutations to the hemagglutinin (HA) proteins of two H3N2 strains, A/Hong Kong/45/2019 and A/Perth/16/2009, affect neutralization by serum from individuals of a variety of ages. The effects of HA mutations on serum neutralization differ across age groups in ways that can be partially rationalized in terms of exposure histories. Mutations that were fixed in influenza variants after 2020 cause greater escape from sera from younger individuals compared with adults. Overall, these results demonstrate that influenza faces distinct antigenic selection regimes from different age groups and suggest approaches to understand how this heterogeneous selection shapes viral evolution.",-1),l=[i,r];function u(h,c,d,f,p,m){return n(),a("div",null,l)}const w=t(s,[["render",u]]);export{_ as __pageData,w as default}; +import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin","date":"2024-07-19","authors":["Frances C Welsh","Rachel T Eguia","Juhye M Lee","Hugh K Haddox","Jared Galloway","Nguyen Van Vinh Chau","Andrea N Loes","John Huddleston","Timothy C Yu","Mai Quynh Le","Nguyen TD Nhat","Nguyen Thi Le Thanh","Alexander L Greninger","Helen Y Chu","Janet A Englund","Trevor Bedford","Frederick A Matsen IV","Maciej F Boni","Jesse D Bloom"],"journal":"Cell Host & Microbe","doi":"10.1016/j.chom.2024.06.015","link":"https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(24)00233-6","image":"/assets/papers/2024_welsh.jpg","keywords":["Influenza","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2024_welsh.md","filePath":"papers/2024_welsh.md"}'),s={name:"papers/2024_welsh.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Human influenza virus evolves to escape neutralization by polyclonal antibodies. 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Overall, these results demonstrate that influenza faces distinct antigenic selection regimes from different age groups and suggest approaches to understand how this heterogeneous selection shapes viral evolution.",-1),l=[i,r];function u(h,c,d,f,p,m){return n(),a("div",null,l)}const w=t(s,[["render",u]]);export{_ as __pageData,w as default}; +import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin","date":"2024-07-19","authors":["Frances C Welsh","Rachel T Eguia","Juhye M Lee","Hugh K Haddox","Jared Galloway","Nguyen Van Vinh Chau","Andrea N Loes","John Huddleston","Timothy C Yu","Mai Quynh Le","Nguyen TD Nhat","Nguyen Thi Le Thanh","Alexander L Greninger","Helen Y Chu","Janet A Englund","Trevor Bedford","Frederick A Matsen IV","Maciej F Boni","Jesse D Bloom"],"journal":"Cell Host & Microbe","doi":"10.1016/j.chom.2024.06.015","link":"https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(24)00233-6","image":"/assets/papers/2024_welsh.jpg","keywords":["Influenza","Deep mutational scanning","Immunity"]},"headers":[],"relativePath":"papers/2024_welsh.md","filePath":"papers/2024_welsh.md"}'),s={name:"papers/2024_welsh.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Human influenza virus evolves to escape neutralization by polyclonal antibodies. 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+import{_ as e,c as t,o,b as n}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Andrew Butler","image":"/assets/people/andrew-butler.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/andrewwbutler","icon":"github"},{"link":"abutler@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/andrew-butler.md","filePath":"people/andrew-butler.md"}'),a={name:"people/andrew-butler.md"},r=n("p",null,"As a postdoc in the Bloom Lab, I am interested in developing and applying single-cell methods to better understand heterogeneity in the context of viral infections.",-1),l=[r];function s(i,d,c,p,u,m){return o(),t("div",null,l)}const b=e(a,[["render",s]]);export{_ as __pageData,b as default}; diff --git a/assets/people_andrew-butler.md.D3xPhRSM.lean.js b/assets/people_andrew-butler.md.DKn4H4UK.lean.js similarity index 92% rename from assets/people_andrew-butler.md.D3xPhRSM.lean.js rename to assets/people_andrew-butler.md.DKn4H4UK.lean.js index 374a080..35922e9 100644 --- a/assets/people_andrew-butler.md.D3xPhRSM.lean.js +++ b/assets/people_andrew-butler.md.DKn4H4UK.lean.js @@ -1 +1 @@ -import{_ as e,c as t,o,b as n}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Andrew Butler","image":"/assets/people/andrew-butler.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/andrewwbutler","icon":"github"},{"link":"abutler@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/andrew-butler.md","filePath":"people/andrew-butler.md"}'),a={name:"people/andrew-butler.md"},r=n("p",null,"As a postdoc in the Bloom Lab, I am interested in developing and applying single-cell methods to better understand heterogeneity in the context of viral infections.",-1),l=[r];function s(i,d,c,p,u,m){return o(),t("div",null,l)}const b=e(a,[["render",s]]);export{_ as __pageData,b as default}; +import{_ as e,c as t,o,b as n}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Andrew Butler","image":"/assets/people/andrew-butler.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/andrewwbutler","icon":"github"},{"link":"abutler@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/andrew-butler.md","filePath":"people/andrew-butler.md"}'),a={name:"people/andrew-butler.md"},r=n("p",null,"As a postdoc in the Bloom Lab, I am interested in developing and applying single-cell methods to better understand heterogeneity in the context of viral infections.",-1),l=[r];function s(i,d,c,p,u,m){return o(),t("div",null,l)}const b=e(a,[["render",s]]);export{_ as __pageData,b as default}; diff --git a/assets/people_arjun-aditham.md.DRXO9Sz2.js b/assets/people_arjun-aditham.md.BhsY8v3S.js similarity index 85% rename from assets/people_arjun-aditham.md.DRXO9Sz2.js rename to assets/people_arjun-aditham.md.BhsY8v3S.js index 59293e3..6f784d7 100644 --- a/assets/people_arjun-aditham.md.DRXO9Sz2.js +++ b/assets/people_arjun-aditham.md.BhsY8v3S.js @@ -1 +1 @@ -import{_ as a,c as t,o as e,b as o}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Arjun Aditham","image":"/assets/people/arjun-aditham.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/arjunaditham","icon":"github"},{"link":"aaditham@fredhutch.org","icon":"email"},{"link":"https://www.linkedin.com/in/arjun-aditham/","icon":"linkedin"}]},"headers":[],"relativePath":"people/arjun-aditham.md","filePath":"people/arjun-aditham.md"}'),n={name:"people/arjun-aditham.md"},i=o("p",null,"As a postdoc in the Bloom Lab, I'm utilizing deep mutational scanning approaches to characterize the Rabies glycoprotein.",-1),s=[i];function r(c,l,d,p,m,h){return e(),t("div",null,s)}const g=a(n,[["render",r]]);export{_ as __pageData,g as default}; 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+import{_ as a,c as e,o as t}from"./chunks/framework.D4bY2S_W.js";const p=JSON.parse('{"title":"Staff Scientist","description":"","frontmatter":{"layout":"person","name":"Caelan Radford","image":"/assets/people/caelan-radford.jpg","title":"Staff Scientist","category":"Staff","links":[{"link":"https://github.com/caelanradford","icon":"github"},{"link":"https://www.linkedin.com/in/caelan-radford-a51b61b3/","icon":"linkedin"},{"link":"ceradfor@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/caelan-radford.md","filePath":"people/caelan-radford.md"}'),n={name:"people/caelan-radford.md"};function o(r,c,i,d,l,s){return t(),e("div")}const m=a(n,[["render",o]]);export{p as __pageData,m as default}; diff --git a/assets/people_caelan-radford.md.B0CVLHQD.lean.js b/assets/people_caelan-radford.md.xo7jW8eT.lean.js similarity index 91% rename from assets/people_caelan-radford.md.B0CVLHQD.lean.js rename to assets/people_caelan-radford.md.xo7jW8eT.lean.js index 2f7d408..4616113 100644 --- a/assets/people_caelan-radford.md.B0CVLHQD.lean.js +++ b/assets/people_caelan-radford.md.xo7jW8eT.lean.js @@ -1 +1 @@ -import{_ as a,c as e,o as t}from"./chunks/framework.BqSDeblO.js";const p=JSON.parse('{"title":"Staff Scientist","description":"","frontmatter":{"layout":"person","name":"Caelan Radford","image":"/assets/people/caelan-radford.jpg","title":"Staff Scientist","category":"Staff","links":[{"link":"https://github.com/caelanradford","icon":"github"},{"link":"https://www.linkedin.com/in/caelan-radford-a51b61b3/","icon":"linkedin"},{"link":"ceradfor@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/caelan-radford.md","filePath":"people/caelan-radford.md"}'),n={name:"people/caelan-radford.md"};function o(r,c,i,d,l,s){return t(),e("div")}const m=a(n,[["render",o]]);export{p as __pageData,m as default}; +import{_ as a,c as e,o as t}from"./chunks/framework.D4bY2S_W.js";const p=JSON.parse('{"title":"Staff Scientist","description":"","frontmatter":{"layout":"person","name":"Caelan Radford","image":"/assets/people/caelan-radford.jpg","title":"Staff Scientist","category":"Staff","links":[{"link":"https://github.com/caelanradford","icon":"github"},{"link":"https://www.linkedin.com/in/caelan-radford-a51b61b3/","icon":"linkedin"},{"link":"ceradfor@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/caelan-radford.md","filePath":"people/caelan-radford.md"}'),n={name:"people/caelan-radford.md"};function o(r,c,i,d,l,s){return t(),e("div")}const m=a(n,[["render",o]]);export{p as __pageData,m as default}; diff --git a/assets/people_caleb-carr.md.B_xWsTZJ.js b/assets/people_caleb-carr.md.DQ-itn5i.js similarity index 84% rename from assets/people_caleb-carr.md.B_xWsTZJ.js rename to assets/people_caleb-carr.md.DQ-itn5i.js index 8ac7b76..d78ca6b 100644 --- a/assets/people_caleb-carr.md.B_xWsTZJ.js +++ b/assets/people_caleb-carr.md.DQ-itn5i.js @@ -1 +1 @@ -import{_ as e,c as a,o as t,b as r}from"./chunks/framework.BqSDeblO.js";const h=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Caleb Carr","image":"/assets/people/caleb-carr.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/Caleb-Carr","icon":"github"},{"link":"ccarr@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/caleb-carr.md","filePath":"people/caleb-carr.md"}'),o={name:"people/caleb-carr.md"},n=r("p",null,"As a graduate student in the Bloom lab, I am using our deep mutational scanning (DMS) pipeline to study the glycoprotein complex of Lassa virus.",-1),c=[n];function s(l,i,p,d,u,m){return t(),a("div",null,c)}const b=e(o,[["render",s]]);export{h as __pageData,b as default}; 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+import{_ as e,c as a,o as t,b as r}from"./chunks/framework.D4bY2S_W.js";const h=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Caleb Carr","image":"/assets/people/caleb-carr.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/Caleb-Carr","icon":"github"},{"link":"ccarr@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/caleb-carr.md","filePath":"people/caleb-carr.md"}'),o={name:"people/caleb-carr.md"},n=r("p",null,"As a graduate student in the Bloom lab, I am using our deep mutational scanning (DMS) pipeline to study the glycoprotein complex of Lassa virus.",-1),c=[n];function s(l,i,p,d,u,m){return t(),a("div",null,c)}const b=e(o,[["render",s]]);export{h as __pageData,b as default}; diff --git a/assets/people_caroline-kikawa.md.Zt4HB2st.js b/assets/people_caroline-kikawa.md.DwYRhm3r.js similarity index 90% rename from assets/people_caroline-kikawa.md.Zt4HB2st.js rename to assets/people_caroline-kikawa.md.DwYRhm3r.js index 667d007..be7a6ad 100644 --- a/assets/people_caroline-kikawa.md.Zt4HB2st.js +++ b/assets/people_caroline-kikawa.md.DwYRhm3r.js @@ -1 +1 @@ -import{_ as a,c as e,o as t}from"./chunks/framework.BqSDeblO.js";const d=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Caroline Kikawa","image":"/assets/people/caroline-kikawa.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/ckikawa","icon":"github"},{"link":"ckikawa@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/caroline-kikawa.md","filePath":"people/caroline-kikawa.md"}'),i={name:"people/caroline-kikawa.md"};function o(n,r,c,l,s,p){return t(),e("div")}const m=a(i,[["render",o]]);export{d as __pageData,m as default}; +import{_ as a,c as e,o as t}from"./chunks/framework.D4bY2S_W.js";const d=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Caroline Kikawa","image":"/assets/people/caroline-kikawa.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/ckikawa","icon":"github"},{"link":"ckikawa@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/caroline-kikawa.md","filePath":"people/caroline-kikawa.md"}'),i={name:"people/caroline-kikawa.md"};function o(n,r,c,l,s,p){return t(),e("div")}const m=a(i,[["render",o]]);export{d as __pageData,m as default}; diff --git a/assets/people_caroline-kikawa.md.Zt4HB2st.lean.js b/assets/people_caroline-kikawa.md.DwYRhm3r.lean.js similarity index 90% rename from assets/people_caroline-kikawa.md.Zt4HB2st.lean.js rename to assets/people_caroline-kikawa.md.DwYRhm3r.lean.js index 667d007..be7a6ad 100644 --- a/assets/people_caroline-kikawa.md.Zt4HB2st.lean.js +++ b/assets/people_caroline-kikawa.md.DwYRhm3r.lean.js @@ -1 +1 @@ -import{_ as a,c as e,o as t}from"./chunks/framework.BqSDeblO.js";const d=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Caroline Kikawa","image":"/assets/people/caroline-kikawa.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/ckikawa","icon":"github"},{"link":"ckikawa@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/caroline-kikawa.md","filePath":"people/caroline-kikawa.md"}'),i={name:"people/caroline-kikawa.md"};function o(n,r,c,l,s,p){return t(),e("div")}const m=a(i,[["render",o]]);export{d as __pageData,m as default}; +import{_ as a,c as e,o as t}from"./chunks/framework.D4bY2S_W.js";const d=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Caroline Kikawa","image":"/assets/people/caroline-kikawa.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/ckikawa","icon":"github"},{"link":"ckikawa@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/caroline-kikawa.md","filePath":"people/caroline-kikawa.md"}'),i={name:"people/caroline-kikawa.md"};function o(n,r,c,l,s,p){return t(),e("div")}const m=a(i,[["render",o]]);export{d as __pageData,m as default}; diff --git a/assets/people_cassandra-simonich.md.oyUdgWQx.js b/assets/people_cassandra-simonich.md.BETrCWbs.js similarity index 86% rename from assets/people_cassandra-simonich.md.oyUdgWQx.js rename to assets/people_cassandra-simonich.md.BETrCWbs.js index 8fccbed..4ea029c 100644 --- a/assets/people_cassandra-simonich.md.oyUdgWQx.js +++ b/assets/people_cassandra-simonich.md.BETrCWbs.js @@ -1 +1 @@ -import{_ as e,c as s,o as a,b as i}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Pediatric Infectious Disease Fellow","description":"","frontmatter":{"layout":"person","name":"Cassandra Simonich","image":"/assets/people/cassandra-simonich.png","title":"Pediatric Infectious Disease Fellow","category":"Postdocs","links":[{"link":"https://github.com/CSimonich","icon":"github"},{"link":"Cassandra.simonich@seattlechildrens.org","icon":"email"}]},"headers":[],"relativePath":"people/cassandra-simonich.md","filePath":"people/cassandra-simonich.md"}'),t={name:"people/cassandra-simonich.md"},o=i("p",null,"Cassie Simonich, MD, PhD is a Pediatric Infectious Diseases Fellow at Seattle Children’s Hospital. 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+import{_ as e,c as i,o as t,b as a}from"./chunks/framework.D4bY2S_W.js";const u=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Sheri Harari","image":"/assets/people/sheri-harari.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/SheriHarari","icon":"github"},{"link":"https://www.linkedin.com/in/sheri-harari-185615166/","icon":"linkedin"},{"link":"https://x.com/SheriHarari","icon":"twitter"},{"link":"sharari@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/sheri-harari.md","filePath":"people/sheri-harari.md"}'),r={name:"people/sheri-harari.md"},o=a("p",null,"Sheri is a postdoc in the Bloom Lab utilizing deep mutational scanning approaches to characterize the HCoV-229E spike glycoprotein.",-1),s=[o];function n(c,l,h,p,d,m){return t(),i("div",null,s)}const g=e(r,[["render",n]]);export{u as __pageData,g as default}; diff --git a/assets/people_teagan-mcmahon.md.BbIi-Ixl.js b/assets/people_teagan-mcmahon.md.DvwHjcmC.js similarity index 89% rename from assets/people_teagan-mcmahon.md.BbIi-Ixl.js rename to assets/people_teagan-mcmahon.md.DvwHjcmC.js index 2912500..db7e502 100644 --- a/assets/people_teagan-mcmahon.md.BbIi-Ixl.js +++ b/assets/people_teagan-mcmahon.md.DvwHjcmC.js @@ -1 +1 @@ -import{_ as e,c as a,o as t}from"./chunks/framework.BqSDeblO.js";const l=JSON.parse('{"title":"Research Technician","description":"","frontmatter":{"layout":"person","name":"Teagan McMahon","image":"/assets/people/teagan-mcmahon.png","title":"Research Technician","category":"Staff","links":[{"link":"https://github.com/tmcmaho","icon":"github"},{"link":"sharari@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/teagan-mcmahon.md","filePath":"people/teagan-mcmahon.md"}'),n={name:"people/teagan-mcmahon.md"};function o(c,r,i,s,m,p){return t(),a("div")}const g=e(n,[["render",o]]);export{l as __pageData,g as default}; +import{_ as e,c as a,o as t}from"./chunks/framework.D4bY2S_W.js";const l=JSON.parse('{"title":"Research Technician","description":"","frontmatter":{"layout":"person","name":"Teagan McMahon","image":"/assets/people/teagan-mcmahon.png","title":"Research Technician","category":"Staff","links":[{"link":"https://github.com/tmcmaho","icon":"github"},{"link":"sharari@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/teagan-mcmahon.md","filePath":"people/teagan-mcmahon.md"}'),n={name:"people/teagan-mcmahon.md"};function o(c,r,i,s,m,p){return t(),a("div")}const g=e(n,[["render",o]]);export{l as __pageData,g as default}; diff --git a/assets/people_teagan-mcmahon.md.BbIi-Ixl.lean.js b/assets/people_teagan-mcmahon.md.DvwHjcmC.lean.js similarity index 89% rename from assets/people_teagan-mcmahon.md.BbIi-Ixl.lean.js rename to assets/people_teagan-mcmahon.md.DvwHjcmC.lean.js index 2912500..db7e502 100644 --- a/assets/people_teagan-mcmahon.md.BbIi-Ixl.lean.js +++ b/assets/people_teagan-mcmahon.md.DvwHjcmC.lean.js @@ -1 +1 @@ -import{_ as e,c as a,o as t}from"./chunks/framework.BqSDeblO.js";const l=JSON.parse('{"title":"Research Technician","description":"","frontmatter":{"layout":"person","name":"Teagan McMahon","image":"/assets/people/teagan-mcmahon.png","title":"Research Technician","category":"Staff","links":[{"link":"https://github.com/tmcmaho","icon":"github"},{"link":"sharari@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/teagan-mcmahon.md","filePath":"people/teagan-mcmahon.md"}'),n={name:"people/teagan-mcmahon.md"};function o(c,r,i,s,m,p){return t(),a("div")}const g=e(n,[["render",o]]);export{l as __pageData,g as default}; +import{_ as e,c as a,o as t}from"./chunks/framework.D4bY2S_W.js";const l=JSON.parse('{"title":"Research Technician","description":"","frontmatter":{"layout":"person","name":"Teagan McMahon","image":"/assets/people/teagan-mcmahon.png","title":"Research Technician","category":"Staff","links":[{"link":"https://github.com/tmcmaho","icon":"github"},{"link":"sharari@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/teagan-mcmahon.md","filePath":"people/teagan-mcmahon.md"}'),n={name:"people/teagan-mcmahon.md"};function o(c,r,i,s,m,p){return t(),a("div")}const g=e(n,[["render",o]]);export{l as __pageData,g as default}; diff --git a/assets/people_tim-yu.md.Cb3Hc4ix.js b/assets/people_tim-yu.md.A1grVJtf.js similarity index 84% rename from assets/people_tim-yu.md.Cb3Hc4ix.js rename to assets/people_tim-yu.md.A1grVJtf.js index cbad34c..53eddef 100644 --- a/assets/people_tim-yu.md.Cb3Hc4ix.js +++ b/assets/people_tim-yu.md.A1grVJtf.js @@ -1 +1 @@ -import{_ as e,c as t,o as n,b as a}from"./chunks/framework.BqSDeblO.js";const h=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Tim Yu","image":"/assets/people/tim-yu.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/timcyu","icon":"github"},{"link":"https://www.linkedin.com/in/timyu316/","icon":"linkedin"},{"link":"timcyu@uw.edu","icon":"email"}]},"headers":[],"relativePath":"people/tim-yu.md","filePath":"people/tim-yu.md"}'),i={name:"people/tim-yu.md"},o=a("p",null,"As a graduate student in the Bloom lab, I use deep mutational scanning to help predict seasonal H3N2 influenza evolution.",-1),s=[o];function l(u,c,p,d,r,m){return n(),t("div",null,s)}const f=e(i,[["render",l]]);export{h as __pageData,f as default}; +import{_ as e,c as t,o as n,b as a}from"./chunks/framework.D4bY2S_W.js";const h=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Tim Yu","image":"/assets/people/tim-yu.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/timcyu","icon":"github"},{"link":"https://www.linkedin.com/in/timyu316/","icon":"linkedin"},{"link":"timcyu@uw.edu","icon":"email"}]},"headers":[],"relativePath":"people/tim-yu.md","filePath":"people/tim-yu.md"}'),i={name:"people/tim-yu.md"},o=a("p",null,"As a graduate student in the Bloom lab, I use deep mutational scanning to help predict seasonal H3N2 influenza evolution.",-1),s=[o];function l(u,c,p,d,r,m){return n(),t("div",null,s)}const f=e(i,[["render",l]]);export{h as __pageData,f as default}; diff --git a/assets/people_tim-yu.md.Cb3Hc4ix.lean.js b/assets/people_tim-yu.md.A1grVJtf.lean.js similarity index 84% rename from assets/people_tim-yu.md.Cb3Hc4ix.lean.js rename to assets/people_tim-yu.md.A1grVJtf.lean.js index cbad34c..53eddef 100644 --- a/assets/people_tim-yu.md.Cb3Hc4ix.lean.js +++ b/assets/people_tim-yu.md.A1grVJtf.lean.js @@ -1 +1 @@ -import{_ as e,c as t,o as n,b as a}from"./chunks/framework.BqSDeblO.js";const h=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Tim Yu","image":"/assets/people/tim-yu.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/timcyu","icon":"github"},{"link":"https://www.linkedin.com/in/timyu316/","icon":"linkedin"},{"link":"timcyu@uw.edu","icon":"email"}]},"headers":[],"relativePath":"people/tim-yu.md","filePath":"people/tim-yu.md"}'),i={name:"people/tim-yu.md"},o=a("p",null,"As a graduate student in the Bloom lab, I use deep mutational scanning to help predict seasonal H3N2 influenza evolution.",-1),s=[o];function l(u,c,p,d,r,m){return n(),t("div",null,s)}const f=e(i,[["render",l]]);export{h as __pageData,f as default}; +import{_ as e,c as t,o as n,b as a}from"./chunks/framework.D4bY2S_W.js";const h=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Tim Yu","image":"/assets/people/tim-yu.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/timcyu","icon":"github"},{"link":"https://www.linkedin.com/in/timyu316/","icon":"linkedin"},{"link":"timcyu@uw.edu","icon":"email"}]},"headers":[],"relativePath":"people/tim-yu.md","filePath":"people/tim-yu.md"}'),i={name:"people/tim-yu.md"},o=a("p",null,"As a graduate student in the Bloom lab, I use deep mutational scanning to help predict seasonal H3N2 influenza evolution.",-1),s=[o];function l(u,c,p,d,r,m){return n(),t("div",null,s)}const f=e(i,[["render",l]]);export{h as __pageData,f as default}; diff --git a/assets/people_wenlin-ren.md.Cu3oo1Mj.js b/assets/people_wenlin-ren.md.BPzf39Md.js similarity index 85% rename from assets/people_wenlin-ren.md.Cu3oo1Mj.js rename to assets/people_wenlin-ren.md.BPzf39Md.js index c99c0cd..a9b6cb9 100644 --- a/assets/people_wenlin-ren.md.Cu3oo1Mj.js +++ b/assets/people_wenlin-ren.md.BPzf39Md.js @@ -1 +1 @@ -import{_ as e,c as n,o as t,b as o}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Wenlin Ren","image":"/assets/people/wenlin-ren.png","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/rwl18","icon":"github"},{"link":"https://www.linkedin.com/in/wenlin-ren/","icon":"linkedin"},{"link":"wren@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/wenlin-ren.md","filePath":"people/wenlin-ren.md"}'),i={name:"people/wenlin-ren.md"},l=o("p",null,"Wenlin is a postdoctoral researcher in the Bloom lab utilizing deep mutation scanning to investigate the entry mechanisms and antigenic evolution of coronaviruses and flaviviruses.",-1),a=[l];function s(r,c,p,d,m,h){return t(),n("div",null,a)}const w=e(i,[["render",s]]);export{_ as __pageData,w as default}; 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+import{_ as e,c as n,o as t,b as o}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Wenlin Ren","image":"/assets/people/wenlin-ren.png","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/rwl18","icon":"github"},{"link":"https://www.linkedin.com/in/wenlin-ren/","icon":"linkedin"},{"link":"wren@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/wenlin-ren.md","filePath":"people/wenlin-ren.md"}'),i={name:"people/wenlin-ren.md"},l=o("p",null,"Wenlin is a postdoctoral researcher in the Bloom lab utilizing deep mutation scanning to investigate the entry mechanisms and antigenic evolution of coronaviruses and flaviviruses.",-1),a=[l];function s(r,c,p,d,m,h){return t(),n("div",null,a)}const w=e(i,[["render",s]]);export{_ as __pageData,w as default}; diff --git a/assets/people_will-hannon.md.B_9BY3GP.js b/assets/people_will-hannon.md.BnukX3BJ.js similarity index 88% rename from assets/people_will-hannon.md.B_9BY3GP.js rename to assets/people_will-hannon.md.BnukX3BJ.js index 26ff078..897f93a 100644 --- a/assets/people_will-hannon.md.B_9BY3GP.js +++ b/assets/people_will-hannon.md.BnukX3BJ.js @@ -1 +1 @@ -import{_ as n,c as e,o as t,b as a}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Data Scientist","description":"","frontmatter":{"layout":"person","name":"Will Hannon","image":"/assets/people/will-hannon.jpg","title":"Data Scientist","category":"Staff","links":[{"link":"https://github.com/WillHannon-MCB","icon":"github"},{"link":"https://www.linkedin.com/in/williamhannon/","icon":"linkedin"},{"link":"whannon@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/will-hannon.md","filePath":"people/will-hannon.md"}'),i={name:"people/will-hannon.md"},o=a("p",null,"As a Data Scientist in the Bloom Lab, I develop and implement computational approaches to study viral evolution and communicate with our data. 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I’m interested in improving access to the information-rich datasets we generate to aid in antigen engineering, therapeutic design, viral surveillance, and gaining a better understanding of viral evolution.",-1),l=[o];function s(r,c,p,d,h,m){return t(),e("div",null,l)}const _=n(i,[["render",s]]);export{g as __pageData,_ as default}; diff --git a/assets/people_will-hannon.md.B_9BY3GP.lean.js b/assets/people_will-hannon.md.BnukX3BJ.lean.js similarity index 88% rename from assets/people_will-hannon.md.B_9BY3GP.lean.js rename to assets/people_will-hannon.md.BnukX3BJ.lean.js index 26ff078..897f93a 100644 --- a/assets/people_will-hannon.md.B_9BY3GP.lean.js +++ b/assets/people_will-hannon.md.BnukX3BJ.lean.js @@ -1 +1 @@ -import{_ as n,c as e,o as t,b as a}from"./chunks/framework.BqSDeblO.js";const g=JSON.parse('{"title":"Data Scientist","description":"","frontmatter":{"layout":"person","name":"Will Hannon","image":"/assets/people/will-hannon.jpg","title":"Data Scientist","category":"Staff","links":[{"link":"https://github.com/WillHannon-MCB","icon":"github"},{"link":"https://www.linkedin.com/in/williamhannon/","icon":"linkedin"},{"link":"whannon@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/will-hannon.md","filePath":"people/will-hannon.md"}'),i={name:"people/will-hannon.md"},o=a("p",null,"As a Data Scientist in the Bloom Lab, I develop and implement computational approaches to study viral evolution and communicate with our data. 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I’m interested in improving access to the information-rich datasets we generate to aid in antigen engineering, therapeutic design, viral surveillance, and gaining a better understanding of viral evolution.",-1),l=[o];function s(r,c,p,d,h,m){return t(),e("div",null,l)}const _=n(i,[["render",s]]);export{g as __pageData,_ as default}; diff --git a/assets/people_xiaohui-ju.md.CQCETETk.js b/assets/people_xiaohui-ju.md.wVgHbx0Q.js similarity index 86% rename from assets/people_xiaohui-ju.md.CQCETETk.js rename to assets/people_xiaohui-ju.md.wVgHbx0Q.js index 0750c9b..85e1741 100644 --- a/assets/people_xiaohui-ju.md.CQCETETk.js +++ b/assets/people_xiaohui-ju.md.wVgHbx0Q.js @@ -1 +1 @@ -import{_ as e,c as o,o as t,b as i}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Xiaohui Ju","image":"/assets/people/xiaohui-ju.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/juxh23","icon":"github"},{"link":"https://www.linkedin.com/in/xiaohui-ju-13b4912a7","icon":"linkedin"},{"link":"xju@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/xiaohui-ju.md","filePath":"people/xiaohui-ju.md"}'),a={name:"people/xiaohui-ju.md"},n=i("p",null,"As a postdoc in Bloom Lab, I utilize deep mutational scanning approaches to characterize the Chikungunya virus envelope protein and non-structural protein in both vertebrate and invertebrate cells.",-1),s=[n];function l(r,c,u,p,h,d){return t(),o("div",null,s)}const x=e(a,[["render",l]]);export{_ as __pageData,x as default}; +import{_ as e,c as o,o as t,b as i}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Xiaohui Ju","image":"/assets/people/xiaohui-ju.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/juxh23","icon":"github"},{"link":"https://www.linkedin.com/in/xiaohui-ju-13b4912a7","icon":"linkedin"},{"link":"xju@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/xiaohui-ju.md","filePath":"people/xiaohui-ju.md"}'),a={name:"people/xiaohui-ju.md"},n=i("p",null,"As a postdoc in Bloom Lab, I utilize deep mutational scanning approaches to characterize the Chikungunya virus envelope protein and non-structural protein in both vertebrate and invertebrate cells.",-1),s=[n];function l(r,c,u,p,h,d){return t(),o("div",null,s)}const x=e(a,[["render",l]]);export{_ as __pageData,x as default}; diff --git a/assets/people_xiaohui-ju.md.CQCETETk.lean.js b/assets/people_xiaohui-ju.md.wVgHbx0Q.lean.js similarity index 86% rename from assets/people_xiaohui-ju.md.CQCETETk.lean.js rename to assets/people_xiaohui-ju.md.wVgHbx0Q.lean.js index 0750c9b..85e1741 100644 --- a/assets/people_xiaohui-ju.md.CQCETETk.lean.js +++ b/assets/people_xiaohui-ju.md.wVgHbx0Q.lean.js @@ -1 +1 @@ -import{_ as e,c as o,o as t,b as i}from"./chunks/framework.BqSDeblO.js";const _=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Xiaohui Ju","image":"/assets/people/xiaohui-ju.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/juxh23","icon":"github"},{"link":"https://www.linkedin.com/in/xiaohui-ju-13b4912a7","icon":"linkedin"},{"link":"xju@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/xiaohui-ju.md","filePath":"people/xiaohui-ju.md"}'),a={name:"people/xiaohui-ju.md"},n=i("p",null,"As a postdoc in Bloom Lab, I utilize deep mutational scanning approaches to characterize the Chikungunya virus envelope protein and non-structural protein in both vertebrate and invertebrate cells.",-1),s=[n];function l(r,c,u,p,h,d){return t(),o("div",null,s)}const x=e(a,[["render",l]]);export{_ as __pageData,x as default}; +import{_ as e,c as o,o as t,b as i}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Xiaohui Ju","image":"/assets/people/xiaohui-ju.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/juxh23","icon":"github"},{"link":"https://www.linkedin.com/in/xiaohui-ju-13b4912a7","icon":"linkedin"},{"link":"xju@fredhutch.org","icon":"email"}]},"headers":[],"relativePath":"people/xiaohui-ju.md","filePath":"people/xiaohui-ju.md"}'),a={name:"people/xiaohui-ju.md"},n=i("p",null,"As a postdoc in Bloom Lab, I utilize deep mutational scanning approaches to characterize the Chikungunya virus envelope protein and non-structural protein in both vertebrate and invertebrate cells.",-1),s=[n];function l(r,c,u,p,h,d){return t(),o("div",null,s)}const x=e(a,[["render",l]]);export{_ as __pageData,x as default}; diff --git a/assets/posts_h5-dms.md.sjbGibHr.js b/assets/posts_h5-dms.md.DJbO7pAW.js similarity index 98% rename from assets/posts_h5-dms.md.sjbGibHr.js rename to assets/posts_h5-dms.md.DJbO7pAW.js index 3a8fe1a..8476efe 100644 --- a/assets/posts_h5-dms.md.sjbGibHr.js +++ b/assets/posts_h5-dms.md.DJbO7pAW.js @@ -1 +1 @@ -import{_ as e,c as a,o as t,g as s,N as r,O as i,P as n,Q as o,R as l,S as h,U as c}from"./chunks/framework.BqSDeblO.js";const H=JSON.parse('{"title":"Deep mutational scanning of H5 influenza hemagglutinin","description":"","frontmatter":{"layout":"post","title":"Deep mutational scanning of H5 influenza hemagglutinin","date":"2024-05-25T00:00:00.000Z","author":"Jesse Bloom"},"headers":[],"relativePath":"posts/h5-dms.md","filePath":"posts/h5-dms.md"}'),u={name:"posts/h5-dms.md"},m=s('

In a new study, we have measured how all mutations to the hemagglutinin (HA) of clade 2.3.4.4b H5 influenza affect molecular phenotypes relevant to pandemic risk. The data can be interactively visualized at https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/

Overview ​

H5 influenza from clade 2.3.4.4b has been causing outbreaks in numerous animals, including wild birds, poultry, cats, and cattle. There is concern that this virus could pose a potential risk to humans if it acquires additional mutations that improve its ability to infect or transmit in humans. From prior work, several molecular phenotypes of HA are known to contribute to pandemic risk.

In a new study led by Bernadeta Dadonaite, we used deep mutational scanning to measure how all HA amino-acid mutations affected key molecular phenotypes.

molecular phenotypes measured

To make these measurements safely, we used a previously described pseudovirus deep mutational scanning system that allows us to characterize the effects of mutations to viral entry proteins using single-cycle replicative lentiviral particles that can be safely studied at biosafety-level 2. Using this system, we made libraries that covered all amino-acid mutations to the current candidate vaccine strain HA for clade 2.3.4.4b H5 influenza.

pseudovirus schematic

First we measured how all mutations affected the ability of HA to mediate cell entry. These results can be visualized either using a heatmap or by projecting functional constraint onto the HA protein structure, as show below. Overall, these measurements identify functionally constrained regions of HA that are unlikely to mutate, and so form good targets for antibodies and other therapeutics.

cell entry heatmapcell entry structure

Next we measured how mutations affect HA's ability to mediate entry into 293T cells that express a2-6 versus a2-3 linked sialic acids, which is important because human transmissible viruses use a2-6. Below are mutations that increase a2-6 usage:

a2-6 usage

We also measured how mutations affect HA stability, which is important as increased HA stability is associated with increased airborne transmissibility. Below is a map of stability enhancing mutations, which tend to be located in helices in the fusion machinery and interfaces between the head and stalk domains:

stability

Finally, we measured how all the mutations affect neutralization by mouse and ferret sera. The key sites of neutralization escape are on the top of the HA head mostly in classically defined antigenic regions, although sites of escape differ a bit between mouse and ferret sera:

escape

To aid in using these data in surveillance, our collaborators (Jordan Ort and Louise Moncla) have integrated them into nextstrain (see here to color a phylogenetic tree by the measured phenotypes).

Angie Hinrichs has also integrated the data into the UShER H5 trees.

How to visualize and access the data ​

To make the data as accessible as possible for use by others, see

See also ​

See also Jesse's Twitter thread and some slides about the study.

',23),d=[m];function p(f,_,g,b,v,y){return t(),a("div",null,d)}const k=e(u,[["render",p]]);export{H as __pageData,k as default}; +import{_ as e,c as a,o as t,g as s,L as r,M as i,N as n,O as o,P as l,Q as h,R as c}from"./chunks/framework.D4bY2S_W.js";const H=JSON.parse('{"title":"Deep mutational scanning of H5 influenza hemagglutinin","description":"","frontmatter":{"layout":"post","title":"Deep mutational scanning of H5 influenza hemagglutinin","date":"2024-05-25T00:00:00.000Z","author":"Jesse Bloom"},"headers":[],"relativePath":"posts/h5-dms.md","filePath":"posts/h5-dms.md"}'),u={name:"posts/h5-dms.md"},m=s('

In a new study, we have measured how all mutations to the hemagglutinin (HA) of clade 2.3.4.4b H5 influenza affect molecular phenotypes relevant to pandemic risk. The data can be interactively visualized at https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/

Overview ​

H5 influenza from clade 2.3.4.4b has been causing outbreaks in numerous animals, including wild birds, poultry, cats, and cattle. There is concern that this virus could pose a potential risk to humans if it acquires additional mutations that improve its ability to infect or transmit in humans. From prior work, several molecular phenotypes of HA are known to contribute to pandemic risk.

In a new study led by Bernadeta Dadonaite, we used deep mutational scanning to measure how all HA amino-acid mutations affected key molecular phenotypes.

molecular phenotypes measured

To make these measurements safely, we used a previously described pseudovirus deep mutational scanning system that allows us to characterize the effects of mutations to viral entry proteins using single-cycle replicative lentiviral particles that can be safely studied at biosafety-level 2. Using this system, we made libraries that covered all amino-acid mutations to the current candidate vaccine strain HA for clade 2.3.4.4b H5 influenza.

pseudovirus schematic

First we measured how all mutations affected the ability of HA to mediate cell entry. These results can be visualized either using a heatmap or by projecting functional constraint onto the HA protein structure, as show below. Overall, these measurements identify functionally constrained regions of HA that are unlikely to mutate, and so form good targets for antibodies and other therapeutics.

cell entry heatmapcell entry structure

Next we measured how mutations affect HA's ability to mediate entry into 293T cells that express a2-6 versus a2-3 linked sialic acids, which is important because human transmissible viruses use a2-6. Below are mutations that increase a2-6 usage:

a2-6 usage

We also measured how mutations affect HA stability, which is important as increased HA stability is associated with increased airborne transmissibility. Below is a map of stability enhancing mutations, which tend to be located in helices in the fusion machinery and interfaces between the head and stalk domains:

stability

Finally, we measured how all the mutations affect neutralization by mouse and ferret sera. The key sites of neutralization escape are on the top of the HA head mostly in classically defined antigenic regions, although sites of escape differ a bit between mouse and ferret sera:

escape

To aid in using these data in surveillance, our collaborators (Jordan Ort and Louise Moncla) have integrated them into nextstrain (see here to color a phylogenetic tree by the measured phenotypes).

Angie Hinrichs has also integrated the data into the UShER H5 trees.

How to visualize and access the data ​

To make the data as accessible as possible for use by others, see

See also ​

See also Jesse's Twitter thread and some slides about the study.

',23),d=[m];function p(f,_,g,b,v,y){return t(),a("div",null,d)}const k=e(u,[["render",p]]);export{H as __pageData,k as default}; diff --git a/assets/posts_h5-dms.md.sjbGibHr.lean.js b/assets/posts_h5-dms.md.DJbO7pAW.lean.js similarity index 79% rename from assets/posts_h5-dms.md.sjbGibHr.lean.js rename to assets/posts_h5-dms.md.DJbO7pAW.lean.js index 0d4f3ab..fe66fed 100644 --- a/assets/posts_h5-dms.md.sjbGibHr.lean.js +++ b/assets/posts_h5-dms.md.DJbO7pAW.lean.js @@ -1 +1 @@ -import{_ as e,c as a,o as t,g as s,N as r,O as i,P as n,Q as o,R as l,S as h,U as c}from"./chunks/framework.BqSDeblO.js";const H=JSON.parse('{"title":"Deep mutational scanning of H5 influenza hemagglutinin","description":"","frontmatter":{"layout":"post","title":"Deep mutational scanning of H5 influenza hemagglutinin","date":"2024-05-25T00:00:00.000Z","author":"Jesse Bloom"},"headers":[],"relativePath":"posts/h5-dms.md","filePath":"posts/h5-dms.md"}'),u={name:"posts/h5-dms.md"},m=s("",23),d=[m];function p(f,_,g,b,v,y){return t(),a("div",null,d)}const k=e(u,[["render",p]]);export{H as __pageData,k as default}; +import{_ as e,c as a,o as t,g as s,L as r,M as i,N as n,O as o,P as l,Q as h,R as c}from"./chunks/framework.D4bY2S_W.js";const H=JSON.parse('{"title":"Deep mutational scanning of H5 influenza hemagglutinin","description":"","frontmatter":{"layout":"post","title":"Deep mutational scanning of H5 influenza hemagglutinin","date":"2024-05-25T00:00:00.000Z","author":"Jesse Bloom"},"headers":[],"relativePath":"posts/h5-dms.md","filePath":"posts/h5-dms.md"}'),u={name:"posts/h5-dms.md"},m=s("",23),d=[m];function p(f,_,g,b,v,y){return t(),a("div",null,d)}const k=e(u,[["render",p]]);export{H as __pageData,k as default}; diff --git a/assets/posts_index.md.B5Aev9pa.js b/assets/posts_index.md.CKU23Rsq.js similarity index 81% rename from assets/posts_index.md.B5Aev9pa.js rename to assets/posts_index.md.CKU23Rsq.js index 5498bf8..5be82b5 100644 --- a/assets/posts_index.md.B5Aev9pa.js +++ b/assets/posts_index.md.CKU23Rsq.js @@ -1 +1 @@ -import{_ as e,c as t,o as s}from"./chunks/framework.BqSDeblO.js";const m=JSON.parse('{"title":"","description":"","frontmatter":{"blog":true},"headers":[],"relativePath":"posts/index.md","filePath":"posts/index.md"}'),o={name:"posts/index.md"};function a(n,r,c,d,i,p){return s(),t("div")}const f=e(o,[["render",a]]);export{m as __pageData,f as default}; +import{_ as e,c as t,o as s}from"./chunks/framework.D4bY2S_W.js";const m=JSON.parse('{"title":"","description":"","frontmatter":{"blog":true},"headers":[],"relativePath":"posts/index.md","filePath":"posts/index.md"}'),o={name:"posts/index.md"};function a(n,r,c,d,i,p){return s(),t("div")}const f=e(o,[["render",a]]);export{m as __pageData,f as default}; diff --git a/assets/posts_index.md.B5Aev9pa.lean.js b/assets/posts_index.md.CKU23Rsq.lean.js similarity index 81% rename from assets/posts_index.md.B5Aev9pa.lean.js rename to assets/posts_index.md.CKU23Rsq.lean.js index 5498bf8..5be82b5 100644 --- a/assets/posts_index.md.B5Aev9pa.lean.js +++ b/assets/posts_index.md.CKU23Rsq.lean.js @@ -1 +1 @@ -import{_ as e,c as t,o as s}from"./chunks/framework.BqSDeblO.js";const m=JSON.parse('{"title":"","description":"","frontmatter":{"blog":true},"headers":[],"relativePath":"posts/index.md","filePath":"posts/index.md"}'),o={name:"posts/index.md"};function a(n,r,c,d,i,p){return s(),t("div")}const f=e(o,[["render",a]]);export{m as __pageData,f as default}; +import{_ as e,c as t,o as s}from"./chunks/framework.D4bY2S_W.js";const m=JSON.parse('{"title":"","description":"","frontmatter":{"blog":true},"headers":[],"relativePath":"posts/index.md","filePath":"posts/index.md"}'),o={name:"posts/index.md"};function a(n,r,c,d,i,p){return s(),t("div")}const f=e(o,[["render",a]]);export{m as __pageData,f as default}; diff --git a/assets/projects_alignparse.md.D2dpYq37.js b/assets/projects_alignparse.md.CBU5zvZR.js similarity index 90% rename from assets/projects_alignparse.md.D2dpYq37.js rename to assets/projects_alignparse.md.CBU5zvZR.js index 99345af..53119f3 100644 --- a/assets/projects_alignparse.md.D2dpYq37.js +++ b/assets/projects_alignparse.md.CBU5zvZR.js @@ -1 +1 @@ -import{_ as t,c as a,o,b as e}from"./chunks/framework.BqSDeblO.js";const h=JSON.parse('{"title":"","description":"","frontmatter":{"layout":"project","name":"alignparse","link":"https://jbloomlab.github.io/alignparse/","github":"https://github.com/jbloomlab/alignparse","documentation":"https://jbloomlab.github.io/alignparse/"},"headers":[],"relativePath":"projects/alignparse.md","filePath":"projects/alignparse.md"}'),s={name:"projects/alignparse.md"},n=e("p",null,"Python package to parse complex user-defined features from long-read PacBio sequencing.",-1),r=e("hr",null,null,-1),l=[n,r];function i(p,c,d,m,u,_){return o(),a("div",null,l)}const b=t(s,[["render",i]]);export{h as __pageData,b as default}; 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+import{_ as t,c as n,o as s,b as e}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"","description":"","frontmatter":{"layout":"project","name":"seqneut-pipeline","link":"https://github.com/jbloomlab/seqneut-pipeline","github":"https://github.com/jbloomlab/seqneut-pipeline","documentation":"https://github.com/jbloomlab/seqneut-pipeline"},"headers":[],"relativePath":"projects/seqneut-pipeline.md","filePath":"projects/seqneut-pipeline.md"}'),o={name:"projects/seqneut-pipeline.md"},i=e("p",null,"Snakemake pipeline for analyzing sequencing-based neutralization assays.",-1),a=e("hr",null,null,-1),p=[i,a];function l(c,r,u,m,_,d){return s(),n("div",null,p)}const f=t(o,[["render",l]]);export{b as __pageData,f as default}; diff --git a/assets/projects_seqneut-pipeline.md.Dg7Co3nS.lean.js b/assets/projects_seqneut-pipeline.md.Ch4cifq3.lean.js similarity index 82% rename from assets/projects_seqneut-pipeline.md.Dg7Co3nS.lean.js rename to assets/projects_seqneut-pipeline.md.Ch4cifq3.lean.js index 6313648..ade8560 100644 --- a/assets/projects_seqneut-pipeline.md.Dg7Co3nS.lean.js +++ b/assets/projects_seqneut-pipeline.md.Ch4cifq3.lean.js @@ -1 +1 @@ -import{_ as t,c as n,o as s,b as e}from"./chunks/framework.BqSDeblO.js";const b=JSON.parse('{"title":"","description":"","frontmatter":{"layout":"project","name":"seqneut-pipeline","link":"https://github.com/jbloomlab/seqneut-pipeline","github":"https://github.com/jbloomlab/seqneut-pipeline","documentation":"https://github.com/jbloomlab/seqneut-pipeline"},"headers":[],"relativePath":"projects/seqneut-pipeline.md","filePath":"projects/seqneut-pipeline.md"}'),o={name:"projects/seqneut-pipeline.md"},i=e("p",null,"Snakemake pipeline for analyzing sequencing-based neutralization assays.",-1),a=e("hr",null,null,-1),p=[i,a];function l(c,r,u,m,_,d){return s(),n("div",null,p)}const f=t(o,[["render",l]]);export{b as __pageData,f as default}; +import{_ as t,c as n,o as s,b as e}from"./chunks/framework.D4bY2S_W.js";const b=JSON.parse('{"title":"","description":"","frontmatter":{"layout":"project","name":"seqneut-pipeline","link":"https://github.com/jbloomlab/seqneut-pipeline","github":"https://github.com/jbloomlab/seqneut-pipeline","documentation":"https://github.com/jbloomlab/seqneut-pipeline"},"headers":[],"relativePath":"projects/seqneut-pipeline.md","filePath":"projects/seqneut-pipeline.md"}'),o={name:"projects/seqneut-pipeline.md"},i=e("p",null,"Snakemake pipeline for analyzing sequencing-based neutralization assays.",-1),a=e("hr",null,null,-1),p=[i,a];function l(c,r,u,m,_,d){return s(),n("div",null,p)}const f=t(o,[["render",l]]);export{b as __pageData,f as default}; diff --git a/assets/research_big-data-and-viruses.md.TC2M2KwD.js b/assets/research_big-data-and-viruses.md.TC2M2KwD.js new file mode 100644 index 0000000..1419aec --- /dev/null +++ b/assets/research_big-data-and-viruses.md.TC2M2KwD.js @@ -0,0 +1 @@ +import{_ as e,c as a,o as t,g as r}from"./chunks/framework.D4bY2S_W.js";const m=JSON.parse('{"title":"Big Datasets and Viral Evolution","description":"","frontmatter":{"title":"Big Datasets and Viral Evolution","color":"pink","order":3},"headers":[],"relativePath":"research/big-data-and-viruses.md","filePath":"research/big-data-and-viruses.md"}'),s={name:"research/big-data-and-viruses.md"},o=r('

We also develop new ways to leverage large datasets to better understand viral evolution.

We have come up with a way to leverage the millions of publicly available SARS-CoV-2 sequences to estimate the effect of individual mutations on viral fitness (see this paper and these slides). We've also created a platform to visualize the mutational effects to aid in interpretation of viral evolution.

We have also integrated thousands of deep mutational scanning measurements into an antibody-escape calculator that was widely used during the SARS-CoV-2 pandemic to understand the antigenic effects of viral mutations.

We also have projects that involve analyzing the evolution of viruses within individual infected humans, and developing models to understand epistasis among viral mutations.

',4),i=[o];function n(l,c,d,p,h,u){return t(),a("div",null,i)}const v=e(s,[["render",n]]);export{m as __pageData,v as default}; diff --git a/assets/research_big-data-and-viruses.md.TC2M2KwD.lean.js b/assets/research_big-data-and-viruses.md.TC2M2KwD.lean.js new file mode 100644 index 0000000..e4f6be2 --- /dev/null +++ b/assets/research_big-data-and-viruses.md.TC2M2KwD.lean.js @@ -0,0 +1 @@ +import{_ as e,c as a,o as t,g as r}from"./chunks/framework.D4bY2S_W.js";const m=JSON.parse('{"title":"Big Datasets and Viral Evolution","description":"","frontmatter":{"title":"Big Datasets and Viral Evolution","color":"pink","order":3},"headers":[],"relativePath":"research/big-data-and-viruses.md","filePath":"research/big-data-and-viruses.md"}'),s={name:"research/big-data-and-viruses.md"},o=r("",4),i=[o];function n(l,c,d,p,h,u){return t(),a("div",null,i)}const v=e(s,[["render",n]]);export{m as __pageData,v as default}; diff --git a/assets/research_deep-mutational-scanning.md.ChHBytu2.js b/assets/research_deep-mutational-scanning.md.ChHBytu2.js new file mode 100644 index 0000000..8657968 --- /dev/null +++ b/assets/research_deep-mutational-scanning.md.ChHBytu2.js @@ -0,0 +1 @@ +import{_ as e,c as a,o as t,g as r,S as n}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Deep Mutational Scanning","description":"","frontmatter":{"title":"Deep Mutational Scanning","color":"sky","order":1},"headers":[],"relativePath":"research/deep-mutational-scanning.md","filePath":"research/deep-mutational-scanning.md"}'),i={name:"research/deep-mutational-scanning.md"},o=r('

Our lab uses deep mutational scanning to experimentally measure how tens-of-thousands of mutations to viral proteins affect key properties including function, immune escape, and receptor binding.

"Pseudovirus neutralization system"

We primarily perform these experiments using a pseudovirus system that allows us to safely characterize mutants of entry proteins from a wide range of viruses, including SARS-CoV-2 spike, influenza hemagglutinin, Lassa virus GPC, HIV envelope, and Nipah virus RBP.

Deep mutational scanning can inform efforts to forecast the evolution of human seasonal viruses and surveil the evolution of potential pandemic viruses. To facilitate the use of deep mutational scanning for these important goals, we develop interactive visualization tools and data analysis pipelines. See here for an example of how we analyze and visualize large datasets to inform the study of viral evolution.

',4),s=[o];function l(c,p,u,f,h,d){return t(),a("div",null,s)}const g=e(i,[["render",l]]);export{_ as __pageData,g as default}; diff --git a/assets/research_deep-mutational-scanning.md.ChHBytu2.lean.js b/assets/research_deep-mutational-scanning.md.ChHBytu2.lean.js new file mode 100644 index 0000000..3a56306 --- /dev/null +++ b/assets/research_deep-mutational-scanning.md.ChHBytu2.lean.js @@ -0,0 +1 @@ +import{_ as e,c as a,o as t,g as r,S as n}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Deep Mutational Scanning","description":"","frontmatter":{"title":"Deep Mutational Scanning","color":"sky","order":1},"headers":[],"relativePath":"research/deep-mutational-scanning.md","filePath":"research/deep-mutational-scanning.md"}'),i={name:"research/deep-mutational-scanning.md"},o=r("",4),s=[o];function l(c,p,u,f,h,d){return t(),a("div",null,s)}const g=e(i,[["render",l]]);export{_ as __pageData,g as default}; diff --git a/assets/research_immunity-and-evolution.md.CARD5jyA.js b/assets/research_immunity-and-evolution.md.CARD5jyA.js new file mode 100644 index 0000000..ebe598e --- /dev/null +++ b/assets/research_immunity-and-evolution.md.CARD5jyA.js @@ -0,0 +1 @@ +import{_ as e,c as t,o as i,g as a,U as n}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Interplay of Immunity and Viral Evolution","description":"","frontmatter":{"title":"Interplay of Immunity and Viral Evolution","color":"indigo","order":2},"headers":[],"relativePath":"research/immunity-and-evolution.md","filePath":"research/immunity-and-evolution.md"}'),o={name:"research/immunity-and-evolution.md"},r=a('

We study immunity and viral evolution at both the population and single-cell levels.

"Sequencing-based neutralization assay"

At the population level, differences in exposure history and immune imprinting lead human individuals to make antibody responses that target different regions of rapidly evolving viruses like influenza and SARS-CoV-2. This population heterogeneity has profound implications for viral evolution and disease susceptibility, as it causes viral mutations to impact the immunity of different individuals differently. We are characterizing this population heterogeneity using both deep mutational scanning and a sequencing based-neutralization assay we developed that increases the throughput of traditional neutralization assays by several orders of magnitude (see schematic at left).

At the single-cell level, we developed approaches to sequence viruses in single cells and quantify how many progeny each infected cell produces. We use these approaches to understand how viral variation impacts the outcome of infection in individual cells.

',4),s=[r];function l(c,d,u,p,h,m){return i(),t("div",null,s)}const v=e(o,[["render",l]]);export{_ as __pageData,v as default}; diff --git a/assets/research_immunity-and-evolution.md.CARD5jyA.lean.js b/assets/research_immunity-and-evolution.md.CARD5jyA.lean.js new file mode 100644 index 0000000..b8feae4 --- /dev/null +++ b/assets/research_immunity-and-evolution.md.CARD5jyA.lean.js @@ -0,0 +1 @@ +import{_ as e,c as t,o as i,g as a,U as n}from"./chunks/framework.D4bY2S_W.js";const _=JSON.parse('{"title":"Interplay of Immunity and Viral Evolution","description":"","frontmatter":{"title":"Interplay of Immunity and Viral Evolution","color":"indigo","order":2},"headers":[],"relativePath":"research/immunity-and-evolution.md","filePath":"research/immunity-and-evolution.md"}'),o={name:"research/immunity-and-evolution.md"},r=a("",4),s=[r];function l(c,d,u,p,h,m){return i(),t("div",null,s)}const v=e(o,[["render",l]]);export{_ as __pageData,v as default}; diff --git a/assets/style.BJoSVSgr.css 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diff --git a/index.html b/index.html index 8032495..9ddd077 100644 --- a/index.html +++ b/index.html @@ -6,19 +6,31 @@ Bloom Lab - + - - - - + + + + -

Welcome to the Bloom Lab

where we study the evolution of Viruses

In the Bloom lab, we study the evolution of viruses and proteins. We use experimental and computational techniques to understand the molecular constraints on viral proteins, and how these constraints shape the capacity of viruses to evolve to escape antibodies, erode pre-existing immunity, and adapt to new hosts.

Our lab is part of the Basic Sciences Divison and the Computational Biology Program at the Fred Hutch. We are also affiliated with the Genome Sciences and Microbiology Departments at the University of Washington, and graduate students often join our lab through the MCB program. Jesse Bloom is an Investigator of the Howard Hughes Medical Institute.

Deep Mutational Scanning

Our lab uses deep mutational scanning to experimentally measure how tens-of-thousands of mutations to viral proteins affect key properties including function, immune escape, and receptor binding.

Example of deep mutational scanning

We primarily perform these experiments using a pseudovirus system that allows us to safely characterize mutants of entry proteins from a wide range of viruses, including SARS-CoV-2 spike, influenza hemagglutinin, Lassa virus GPC, HIV envelope, and Nipah virus RBP.

Deep mutational scanning can inform efforts to forecast the evolution of human seasonal viruses and surveil the evolution of potential pandemic viruses. To facilitate the use of deep mutational scanning for these important goals, we develop interactive visualization tools and data analysis pipelines. See here for an example of how we analyze and visualize large datasets to inform the study of viral evolution.

Interplay of Immunity and Viral Evolution

We study immunity and viral evolution at both the population and single-cell levels.

Description

At the population level, differences in exposure history and immune imprinting lead human individuals to make antibody responses that target different regions of rapidly evolving viruses like influenza and SARS-CoV-2. This population heterogeneity has profound implications for viral evolution and disease susceptibility, as it causes viral mutations to impact the immunity of different individuals differently. We are characterizing this population heterogeneity using both deep mutational scanning and a sequencing based-neutralization assay we developed that increases the throughput of traditional neutralization assays by several orders of magnitude (see schematic at left).

At the single-cell level, we developed approaches to sequence viruses in single cells and quantify how many progeny each infected cell produces. We use these approaches to understand how viral variation impacts the outcome of infection in individual cells.

Big Datasets and Viral Evolution

We also develop new ways to leverage large datasets to better understand viral evolution.

We have come up with a way to leverage the millions of publicly available SARS-CoV-2 sequences to estimate the effect of individual mutations on viral fitness (see this paper and these slides). We've also created a platform to visualize the mutational effects to aid in interpretation of viral evolution.

We have also integrated thousands of deep mutational scanning measurements into an antibody-escape calculator that was widely used during the SARS-CoV-2 pandemic to understand the antigenic effects of viral mutations.

We also have projects that involve analyzing the evolution of viruses within individual infected humans, and developing models to understand epistasis among viral mutations.

Copyright © Jesse Bloom 2024-Present

- +

Welcome to the Bloom Lab

where we study the evolution of Viruses

In the Bloom lab, we study the evolution of viruses and proteins. We use experimental and computational techniques to understand the molecular constraints on viral proteins, and how these constraints shape the capacity of viruses to evolve to escape antibodies, erode pre-existing immunity, and adapt to new hosts.

Our lab is part of the Basic Sciences Divison and the Computational Biology Program at the Fred Hutch. We are also affiliated with the Genome Sciences and Microbiology Departments at the University of Washington, and graduate students often join our lab through the MCB program. Jesse Bloom is an Investigator of the Howard Hughes Medical Institute.

Scroll down to learn more

Deep Mutational Scanning

Our lab uses deep mutational scanning to experimentally measure how tens-of-thousands of mutations to viral proteins affect key properties including function, immune escape, and receptor binding.

+

"Pseudovirus neutralization system"

+

We primarily perform these experiments using a pseudovirus system that allows us to safely characterize mutants of entry proteins from a wide range of viruses, including SARS-CoV-2 spike, influenza hemagglutinin, Lassa virus GPC, HIV envelope, and Nipah virus RBP.

+

Deep mutational scanning can inform efforts to forecast the evolution of human seasonal viruses and surveil the evolution of potential pandemic viruses. To facilitate the use of deep mutational scanning for these important goals, we develop interactive visualization tools and data analysis pipelines. See here for an example of how we analyze and visualize large datasets to inform the study of viral evolution.

+

Interplay of Immunity and Viral Evolution

We study immunity and viral evolution at both the population and single-cell levels.

+

"Sequencing-based neutralization assay"

+

At the population level, differences in exposure history and immune imprinting lead human individuals to make antibody responses that target different regions of rapidly evolving viruses like influenza and SARS-CoV-2. This population heterogeneity has profound implications for viral evolution and disease susceptibility, as it causes viral mutations to impact the immunity of different individuals differently. We are characterizing this population heterogeneity using both deep mutational scanning and a sequencing based-neutralization assay we developed that increases the throughput of traditional neutralization assays by several orders of magnitude (see schematic at left).

+

At the single-cell level, we developed approaches to sequence viruses in single cells and quantify how many progeny each infected cell produces. We use these approaches to understand how viral variation impacts the outcome of infection in individual cells.

+

Big Datasets and Viral Evolution

We also develop new ways to leverage large datasets to better understand viral evolution.

+

We have come up with a way to leverage the millions of publicly available SARS-CoV-2 sequences to estimate the effect of individual mutations on viral fitness (see this paper and these slides). We've also created a platform to visualize the mutational effects to aid in interpretation of viral evolution.

+

We have also integrated thousands of deep mutational scanning measurements into an antibody-escape calculator that was widely used during the SARS-CoV-2 pandemic to understand the antigenic effects of viral mutations.

+

We also have projects that involve analyzing the evolution of viruses within individual infected humans, and developing models to understand epistasis among viral mutations.

+

Copyright © Jesse Bloom 2024-Present

+ \ No newline at end of file diff --git a/papers/2013_ashenberg.html b/papers/2013_ashenberg.html index dbfc5b7..e989fd3 100644 --- a/papers/2013_ashenberg.html +++ b/papers/2013_ashenberg.html @@ -6,19 +6,19 @@ Mutational effects on stability are largely conserved during protein evolution | Bloom Lab - + - - - - + + + +
PNASDecember 24, 2013

Mutational effects on stability are largely conserved during protein evolution

Orr Ashenberg, Lizhi Ian Gong, Jesse D Bloom
doi:10.1073/pnas.1314781111

Abstract ​

Protein stability and folding are the result of cooperative interactions among many residues, yet phylogenetic approaches assume that sites are independent. This discrepancy has engendered concerns about large evolutionary shifts in mutational effects that might confound phylogenetic approaches. Here we experimentally investigate this issue by introducing the same mutations into a set of diverged homologs of the influenza nucleoprotein and measuring the effects on stability. We find that mutational effects on stability are largely conserved across the homologs. We reach qualitatively similar conclusions when we simulate protein evolution with molecular-mechanics force fields. Our results do not mean that proteins evolve without epistasis, which can still arise even when mutational stability effects are conserved. However, our findings indicate that large evolutionary shifts in mutational effects on stability are rare, at least among homologs with similar structures and functions. We suggest that properly describing the clearly observable and highly conserved amino acid preferences at individual sites is likely to be far more important for phylogenetic analyses than accounting for rare shifts in amino acid propensities due to site covariation.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2013_gong.html b/papers/2013_gong.html index 147f853..f0d2aec 100644 --- a/papers/2013_gong.html +++ b/papers/2013_gong.html @@ -6,19 +6,19 @@ Stability-mediated epistasis constrains the evolution of an influenza protein | Bloom Lab - + - - - - + + + +
Journal of virologyMay 14, 2013

Stability-mediated epistasis constrains the evolution of an influenza protein

Lizhi Ian Gong, Marc A Suchard, Jesse D Bloom
doi:10.7554/eLife.00631.001

Abstract ​

John Maynard Smith compared protein evolution to the game where one word is converted into another a single letter at a time, with the constraint that all intermediates are words: WORD→WORE→GORE→GONE→GENE. In this analogy, epistasis constrains evolution, with some mutations tolerated only after the occurrence of others. To test whether epistasis similarly constrains actual protein evolution, we created all intermediates along a 39-mutation evolutionary trajectory of influenza nucleoprotein, and also introduced each mutation individually into the parent. Several mutations were deleterious to the parent despite becoming fixed during evolution without negative impact. These mutations were destabilizing, and were preceded or accompanied by stabilizing mutations that alleviated their adverse effects. The constrained mutations occurred at sites enriched in T-cell epitopes, suggesting they promote viral immune escape. Our results paint a coherent portrait of epistasis during nucleoprotein evolution, with stabilizing mutations permitting otherwise inaccessible destabilizing mutations which are sometimes of adaptive value.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2013_hooper.html b/papers/2013_hooper.html index 49fe02b..884cf07 100644 --- a/papers/2013_hooper.html +++ b/papers/2013_hooper.html @@ -6,19 +6,19 @@ A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein | Bloom Lab - + - - - - + + + +
Journal of virologyDecember 1, 2013

A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein

Kathryn A Hooper, Jesse D Bloom
doi:10.1128/jvi.01889-13

Abstract ​

In the vast majority of influenza A viruses characterized to date, hemagglutinin (HA) is the receptor-binding and fusion protein, whereas neuraminidase (NA) is a receptor-cleaving protein that facilitates viral release but is expendable for entry. However, the NAs of some recent human H3N2 isolates have acquired receptor-binding activity via the mutation D151G, although these isolates also appear to retain the ability to bind receptors via HA. We report here the laboratory generation of a mutation (G147R) that enables an N1 NA to completely co-opt the receptor-binding function normally performed by HA. Viruses with this mutant NA grow to high titers even in the presence of extensive mutations to conserved residues in HA's receptor-binding pocket. When the receptor-binding NA is paired with this binding-deficient HA, viral infectivity and red blood cell agglutination are blocked by NA inhibitors. Furthermore, virus-like particles expressing only the receptor-binding NA agglutinate red blood cells in an NA-dependent manner. Although the G147R NA receptor-binding mutant virus that we characterize is a laboratory creation, this same mutation is found in several natural clusters of H1N1 and H5N1 viruses. Our results demonstrate that, at least in tissue culture, influenza virus receptor-binding activity can be entirely shifted from HA to NA.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2014_bloom_a.html b/papers/2014_bloom_a.html index 760cf82..633d603 100644 --- a/papers/2014_bloom_a.html +++ b/papers/2014_bloom_a.html @@ -6,19 +6,19 @@ An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs | Bloom Lab - + - - - - + + + +
Molecular biology and evolutionOctober 1, 2014

An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs

Jesse D Bloom
doi:10.1093/molbev/msu220

Abstract ​

Phylogenetic analyses of molecular data require a quantitative model for how sequences evolve. Traditionally, the details of the site-specific selection that governs sequence evolution are not known a priori, making it challenging to create evolutionary models that adequately capture the heterogeneity of selection at different sites. However, recent advances in high-throughput experiments have made it possible to quantify the effects of all single mutations on gene function. I have previously shown that such high-throughput experiments can be combined with knowledge of underlying mutation rates to create a parameter-free evolutionary model that describes the phylogeny of influenza nucleoprotein far better than commonly used existing models. Here, I extend this work by showing that published experimental data on TEM-1 beta-lactamase (Firnberg E, Labonte JW, Gray JJ, Ostermeier M. 2014. A comprehensive, high-resolution map of a gene’s fitness landscape. Mol Biol Evol. 31:1581–1592) can be combined with a few mutation rate parameters to create an evolutionary model that describes beta-lactamase phylogenies much better than most common existing models. This experimentally informed evolutionary model is superior even for homologs that are substantially diverged (about 35% divergence at the protein level) from the TEM-1 parent that was the subject of the experimental study. These results suggest that experimental measurements can inform phylogenetic evolutionary models that are applicable to homologs that span a substantial range of sequence divergence.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2014_bloom_b.html b/papers/2014_bloom_b.html index 54416ad..54b393e 100644 --- a/papers/2014_bloom_b.html +++ b/papers/2014_bloom_b.html @@ -6,19 +6,19 @@ An experimentally determined evolutionary model dramatically improves phylogenetic fit | Bloom Lab - + - - - - + + + +
Molecular Biology and EvolutionAugust 1, 2014

An experimentally determined evolutionary model dramatically improves phylogenetic fit

Jesse D Bloom
doi:10.1093/molbev/msu173

Abstract ​

All modern approaches to molecular phylogenetics require a quantitative model for how genes evolve. Unfortunately, existing evolutionary models do not realistically represent the site-heterogeneous selection that governs actual sequence change. Attempts to remedy this problem have involved augmenting these models with a burgeoning number of free parameters. Here, I demonstrate an alternative: Experimental determination of a parameter-free evolutionary model via mutagenesis, functional selection, and deep sequencing. Using this strategy, I create an evolutionary model for influenza nucleoprotein that describes the gene phylogeny far better than existing models with dozens or even hundreds of free parameters. Emerging high-throughput experimental strategies such as the one employed here provide fundamentally new information that has the potential to transform the sensitivity of phylogenetic and genetic analyses.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2014_gong.html b/papers/2014_gong.html index 0c1718f..c792f43 100644 --- a/papers/2014_gong.html +++ b/papers/2014_gong.html @@ -6,19 +6,19 @@ Epistatically interacting substitutions are enriched during adaptive protein evolution | Bloom Lab - + - - - - + + + +
PLoS geneticsMay 8, 2014

Epistatically interacting substitutions are enriched during adaptive protein evolution

Lizhi Ian Gong, Jesse D Bloom
doi:10.1371/journal.pgen.1004328

Abstract ​

Most experimental studies of epistasis in evolution have focused on adaptive changes—but adaptation accounts for only a portion of total evolutionary change. Are the patterns of epistasis during adaptation representative of evolution more broadly? We address this question by examining a pair of protein homologs, of which only one is subject to a well-defined pressure for adaptive change. Specifically, we compare the nucleoproteins from human and swine influenza. Human influenza is under continual selection to evade recognition by acquired immune memory, while swine influenza experiences less such selection due to the fact that pigs are less likely to be infected with influenza repeatedly in a lifetime. Mutations in some types of immune epitopes are therefore much more strongly adaptive to human than swine influenza—here we focus on epitopes targeted by human cytotoxic T lymphocytes. The nucleoproteins of human and swine influenza possess nearly identical numbers of such epitopes. However, mutations in these epitopes are fixed significantly more frequently in human than in swine influenza, presumably because these epitope mutations are adaptive only to human influenza. Experimentally, we find that epistatically constrained mutations are fixed only in the adaptively evolving human influenza lineage, where they occur at sites that are enriched in epitopes. Overall, our results demonstrate that epistatically interacting substitutions are enriched during adaptation, suggesting that the prevalence of epistasis is dependent on the underlying evolutionary forces at play.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2014_thyagarajan.html b/papers/2014_thyagarajan.html index 6ba7264..eaf1588 100644 --- a/papers/2014_thyagarajan.html +++ b/papers/2014_thyagarajan.html @@ -6,19 +6,19 @@ The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin | Bloom Lab - + - - - - + + + +
eLifeJuly 8, 2014

The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin

Bargavi Thyagarajan, Jesse D Bloom
doi:10.7554/eLife.03300

Abstract ​

Influenza is notable for its evolutionary capacity to escape immunity targeting the viral hemagglutinin. We used deep mutational scanning to examine the extent to which a high inherent mutational tolerance contributes to this antigenic evolvability. We created mutant viruses that incorporate most of the ≈104 amino-acid mutations to hemagglutinin from A/WSN/1933 (H1N1) influenza. After passaging these viruses in tissue culture to select for functional variants, we used deep sequencing to quantify mutation frequencies before and after selection. These data enable us to infer the preference for each amino acid at each site in hemagglutinin. These inferences are consistent with existing knowledge about the protein's structure and function, and can be used to create a model that describes hemagglutinin's evolution far better than existing phylogenetic models. We show that hemagglutinin has a high inherent tolerance for mutations at antigenic sites, suggesting that this is one factor contributing to influenza's antigenic evolution.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2015_bloom.html b/papers/2015_bloom.html index 6e661da..a9d06f9 100644 --- a/papers/2015_bloom.html +++ b/papers/2015_bloom.html @@ -6,19 +6,19 @@ Software for the analysis and visualization of deep mutational scanning data | Bloom Lab - + - - - - + + + +
BMC bioinformaticsDecember 1, 2015

Software for the analysis and visualization of deep mutational scanning data

Jesse D Bloom
doi:10.1186/s12859-015-0590-4

Abstract ​

Deep mutational scanning is a technique to estimate the impacts of mutations on a gene by using deep sequencing to count mutations in a library of variants before and after imposing a functional selection. The impacts of mutations must be inferred from changes in their counts after selection.

I describe a software package, dms_tools, to infer the impacts of mutations from deep mutational scanning data using a likelihood-based treatment of the mutation counts. I show that dms_tools yields more accurate inferences on simulated data than simply calculating ratios of counts pre- and post-selection. Using dms_tools, one can infer the preference of each site for each amino acid given a single selection pressure, or assess the extent to which these preferences change under different selection pressures.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2015_doud.html b/papers/2015_doud.html index b93f6ac..31825d7 100644 --- a/papers/2015_doud.html +++ b/papers/2015_doud.html @@ -6,19 +6,19 @@ Site-specific amino acid preferences are mostly conserved in two closely related protein homologs | Bloom Lab - + - - - - + + + +
Molecular biology and evolutionNovember 1, 2015

Site-specific amino acid preferences are mostly conserved in two closely related protein homologs

Michael B Doud, Orr Ashenberg, Jesse D Bloom
doi:10.1093/molbev/msv167

Abstract ​

Evolution drives changes in a protein’s sequence over time. The extent to which these changes in sequence lead to shifts in the underlying preference for each amino acid at each site is an important question with implications for comparative sequence-analysis methods, such as molecular phylogenetics. To quantify the extent that site-specific amino acid preferences shift during evolution, we performed deep mutational scanning on two homologs of human influenza nucleoprotein with 94% amino acid identity. We found that only a modest fraction of sites exhibited shifts in amino acid preferences that exceeded the noise in our experiments. Furthermore, even among sites that did exhibit detectable shifts, the magnitude tended to be small relative to differences between nonhomologous proteins. Given the limited change in amino acid preferences between these close homologs, we tested whether our measurements could inform site-specific substitution models that describe the evolution of nucleoproteins from more diverse influenza viruses. We found that site-specific evolutionary models informed by our experiments greatly outperformed nonsite-specific alternatives in fitting phylogenies of nucleoproteins from human, swine, equine, and avian influenza. Combining the experimental data from both homologs improved phylogenetic fit, partly because measurements in multiple genetic contexts better captured the evolutionary average of the amino acid preferences for sites with shifting preferences. Our results show that site-specific amino acid preferences are sufficiently conserved that measuring mutational effects in one protein provides information that can improve quantitative evolutionary modeling of nearby homologs.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2015_hooper.html b/papers/2015_hooper.html index 3067928..678b561 100644 --- a/papers/2015_hooper.html +++ b/papers/2015_hooper.html @@ -6,19 +6,19 @@ Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice | Bloom Lab - + - - - - + + + +
Journal of virologyApril 1, 2015

Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice

Kathryn A Hooper, James E Crowe Jr, Jesse D Bloom
doi:10.1128/jvi.00012-15

Abstract ​

In nearly all characterized influenza viruses, hemagglutinin (HA) is the receptor-binding protein while neuraminidase (NA) is a receptor-cleaving protein that aids in viral release. However, in recent years, several groups have described point mutations that confer receptor-binding activity on NA, albeit in laboratory rather than natural settings. One of these mutations, D151G, appears to arise in the NA of recent human H3N2 viruses upon passage in tissue culture. We inadvertently isolated the second of these mutations, G147R, in the NA of the lab-adapted A/WSN/33 (H1N1) strain while we were passaging a heavily engineered virus in the lab. G147R also occurs at low frequencies in the reported sequences of viruses from three different lineages: human 2009 pandemic H1N1 (pdmH1N1), human seasonal H1N1, and chicken H5N1. Here we reconstructed a representative G147R NA from each of these lineages and found that all of the proteins have acquired the ability to bind an unknown cellular receptor while retaining substantial sialidase activity. We then reconstructed a virus with the HA and NA of a reported G147R pdmH1N1 variant and found no attenuation of viral replication in cell culture or change in pathogenesis in mice. Furthermore, the G147R virus had modestly enhanced resistance to neutralization by the Fab of an antibody against the receptor-binding pocket of HA, although it remained completely sensitive to the full-length IgG. Overall, our results suggest that circulating N1 viruses occasionally may acquire the G147R NA receptor-binding mutation without impairment of replicative capacity.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2015_machkovech.html b/papers/2015_machkovech.html index 4a60932..2281898 100644 --- a/papers/2015_machkovech.html +++ b/papers/2015_machkovech.html @@ -6,19 +6,19 @@ Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages | Bloom Lab - + - - - - + + + +
Journal of virologyNovember 15, 2015

Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages

Heather M Machkovech, Trevor Bedford, Marc A Suchard, Jesse D Bloom
doi:10.1128/jvi.01571-15

Abstract ​

Numerous experimental studies have demonstrated that CD8+ T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8+ T cells. Here we use a novel computational approach to test for selection in CD8+ T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8+ T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8+ T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8+ T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2016_doud.html b/papers/2016_doud.html index 129f7c4..0737690 100644 --- a/papers/2016_doud.html +++ b/papers/2016_doud.html @@ -6,19 +6,19 @@ Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin | Bloom Lab - + - - - - + + + +
VirusesJune 3, 2016

Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin

Michael B Doud, Jesse D Bloom
doi:10.3390/v8060155

Abstract ​

Influenza genes evolve mostly via point mutations, and so knowing the effect of every amino-acid mutation provides information about evolutionary paths available to the virus. We and others have combined high-throughput mutagenesis with deep sequencing to estimate the effects of large numbers of mutations to influenza genes. However, these measurements have suffered from substantial experimental noise due to a variety of technical problems, the most prominent of which is bottlenecking during the generation of mutant viruses from plasmids. Here we describe advances that ameliorate these problems, enabling us to measure with greatly improved accuracy and reproducibility the effects of all amino-acid mutations to an H1 influenza hemagglutinin on viral replication in cell culture. The largest improvements come from using a helper virus to reduce bottlenecks when generating viruses from plasmids. Our measurements confirm at much higher resolution the results of previous studies suggesting that antigenic sites on the globular head of hemagglutinin are highly tolerant of mutations. We also show that other regions of hemagglutinin—including the stalk epitopes targeted by broadly neutralizing antibodies—have a much lower inherent capacity to tolerate point mutations. The ability to accurately measure the effects of all influenza mutations should enhance efforts to understand and predict viral evolution.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2016_haddox.html b/papers/2016_haddox.html index 749ed7d..e0046b7 100644 --- a/papers/2016_haddox.html +++ b/papers/2016_haddox.html @@ -6,19 +6,19 @@ Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture | Bloom Lab - + - - - - + + + +
PLoS pathogensDecember 13, 2016

Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture

Hugh K Haddox, Adam S Dingens, Jesse D Bloom
doi:10.1371/journal.ppat.1006114

Abstract ​

HIV is notorious for its capacity to evade immunity and anti-viral drugs through rapid sequence evolution. Knowledge of the functional effects of mutations to HIV is critical for understanding this evolution. HIV’s most rapidly evolving protein is its envelope (Env). Here we use deep mutational scanning to experimentally estimate the effects of all amino-acid mutations to Env on viral replication in cell culture. Most mutations are under purifying selection in our experiments, although a few sites experience strong selection for mutations that enhance HIV’s replication in cell culture. We compare our experimental measurements of each site’s preference for each amino acid to the actual frequencies of these amino acids in naturally occurring HIV sequences. Our measured amino-acid preferences correlate with amino-acid frequencies in natural sequences for most sites. However, our measured preferences are less concordant with natural amino-acid frequencies at surface-exposed sites that are subject to pressures absent from our experiments such as antibody selection. Our data enable us to quantify the inherent mutational tolerance of each site in Env. We show that the epitopes of broadly neutralizing antibodies have a significantly reduced inherent capacity to tolerate mutations, rigorously validating a pervasive idea in the field. Overall, our results help disentangle the role of inherent functional constraints and external selection pressures in shaping Env’s evolution.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2016_xue.html b/papers/2016_xue.html index 2432daf..4b49686 100644 --- a/papers/2016_xue.html +++ b/papers/2016_xue.html @@ -6,19 +6,19 @@ Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture | Bloom Lab - + - - - - + + + +
eLifeMarch 15, 2016

Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture

Katherine S Xue, Kathryn A Hooper, Anja R Ollodart, Adam S Dingens, Jesse D Bloom
doi:10.7554/eLife.13974.001

Abstract ​

RNA viruses rapidly diversify into quasispecies of related genotypes. This genetic diversity has long been known to facilitate adaptation, but recent studies have suggested that cooperation between variants might also increase population fitness. Here, we demonstrate strong cooperation between two H3N2 influenza variants that differ by a single mutation at residue 151 in neuraminidase, which normally mediates viral exit from host cells. Residue 151 is often annotated as an ambiguous amino acid in sequenced isolates, indicating mixed viral populations. We show that mixed populations grow better than either variant alone in cell culture. Pure populations of either variant generate the other through mutation and then stably maintain a mix of the two genotypes. We suggest that cooperation arises because mixed populations combine one variant’s proficiency at cell entry with the other’s proficiency at cell exit. Our work demonstrates a specific cooperative interaction between defined variants in a viral quasispecies.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2017_ashenberg.html b/papers/2017_ashenberg.html index 89a6c4b..fabd483 100644 --- a/papers/2017_ashenberg.html +++ b/papers/2017_ashenberg.html @@ -6,19 +6,19 @@ Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA | Bloom Lab - + - - - - + + + +
PLoS pathogensMarch 27, 2017

Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA

Orr Ashenberg, Jai Padmakumar, Michael B Doud, Jesse D Bloom
doi:10.1371/journal.ppat.1006288

Abstract ​

The innate-immune restriction factor MxA inhibits influenza replication by targeting the viral nucleoprotein (NP). Human influenza virus is more resistant than avian influenza virus to inhibition by human MxA, and prior work has compared human and avian viral strains to identify amino-acid differences in NP that affect sensitivity to MxA. However, this strategy is limited to identifying sites in NP where mutations that affect MxA sensitivity have fixed during the small number of documented zoonotic transmissions of influenza to humans. Here we use an unbiased deep mutational scanning approach to quantify how all single amino-acid mutations to NP affect MxA sensitivity in the context of replication-competent virus. We both identify new sites in NP where mutations affect MxA resistance and re-identify mutations known to have increased MxA resistance during historical adaptations of influenza to humans. Most of the sites where mutations have the greatest effect are almost completely conserved across all influenza A viruses, and the amino acids at these sites confer relatively high resistance to MxA. These sites cluster in regions of NP that appear to be important for its recognition by MxA. Overall, our work systematically identifies the sites in influenza nucleoprotein where mutations affect sensitivity to MxA. We also demonstrate a powerful new strategy for identifying regions of viral proteins that affect inhibition by host factors.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2017_bloom.html b/papers/2017_bloom.html index f6017a1..ac66f32 100644 --- a/papers/2017_bloom.html +++ b/papers/2017_bloom.html @@ -6,19 +6,19 @@ Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models | Bloom Lab - + - - - - + + + +
Biology directDecember 1, 2017

Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models

Jesse D Bloom
doi:10.1186/s13062-016-0172-z

Abstract ​

Sites of positive selection are identified by comparing observed evolutionary patterns to those expected under a null model for evolution in the absence of such selection. For protein-coding genes, the most common null model is that nonsynonymous and synonymous mutations fix at equal rates; this unrealistic model has limited power to detect many interesting forms of selection.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2017_dingens.html b/papers/2017_dingens.html index e11f727..f797617 100644 --- a/papers/2017_dingens.html +++ b/papers/2017_dingens.html @@ -6,19 +6,19 @@ Comprehensive mapping of HIV-1 escape from a broadly neutralizing antibody | Bloom Lab - + - - - - + + + +
Cell host & microbeJune 14, 2017

Comprehensive mapping of HIV-1 escape from a broadly neutralizing antibody

Adam S Dingens, Hugh K Haddox, Julie Overbaugh, Jesse D Bloom
doi:10.1016/j.chom.2017.05.003

Abstract ​

Precisely defining how viral mutations affect HIV’s sensitivity to antibodies is vital to develop and evaluate vaccines and antibody immunotherapeutics. Despite great effort, a full map of escape mutants has not been delineated for an anti-HIV antibody. We describe a massively parallel experimental approach to quantify how all single amino acid mutations to HIV Envelope (Env) affect neutralizing antibody sensitivity in the context of replication-competent virus. We apply this approach to PGT151, a broadly neutralizing antibody recognizing a combination of Env residues and glycans. We confirm sites previously defined by structural and functional studies and reveal additional sites of escape, such as positively charged mutations in the antibody-Env interface. Evaluating the effect of each amino acid at each site lends insight into biochemical mechanisms of escape throughout the epitope, highlighting roles for charge-charge repulsions. Thus, comprehensively mapping HIV antibody escape gives a quantitative, mutation-level view of Env evasion of neutralization.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2017_doud.html b/papers/2017_doud.html index 3d30d53..24e1ecf 100644 --- a/papers/2017_doud.html +++ b/papers/2017_doud.html @@ -6,19 +6,19 @@ Complete mapping of viral escape from neutralizing antibodies | Bloom Lab - + - - - - + + + +
PLoS pathogensMarch 13, 2017

Complete mapping of viral escape from neutralizing antibodies

Michael B Doud, Scott E Hensley, Jesse D Bloom
doi:10.1371/journal.ppat.1006271

Abstract ​

Identifying viral mutations that confer escape from antibodies is crucial for understanding the interplay between immunity and viral evolution. We describe a high-throughput approach to quantify the selection that monoclonal antibodies exert on all single amino-acid mutations to a viral protein. This approach, mutational antigenic profiling, involves creating all replication-competent protein variants of a virus, selecting with antibody, and using deep sequencing to identify enriched mutations. We use mutational antigenic profiling to comprehensively identify mutations that enable influenza virus to escape four monoclonal antibodies targeting hemagglutinin, and validate key findings with neutralization assays. We find remarkable mutation-level idiosyncrasy in antibody escape: for instance, at a single residue targeted by two antibodies, some mutations escape both antibodies while other mutations escape only one or the other. Because mutational antigenic profiling rapidly maps all mutations selected by an antibody, it is useful for elucidating immune specificities and interpreting the antigenic consequences of viral genetic variation.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2017_hilton.html b/papers/2017_hilton.html index 1bda9bd..af8452e 100644 --- a/papers/2017_hilton.html +++ b/papers/2017_hilton.html @@ -6,19 +6,19 @@ phydms: Software for phylogenetic analyses informed by deep mutational scanning | Bloom Lab - + - - - - + + + +
PeerJJuly 31, 2017

phydms: Software for phylogenetic analyses informed by deep mutational scanning

Sarah K Hilton, Michael B Doud, Jesse D Bloom
doi:10.7717/peerj.3657

Abstract ​

It has recently become possible to experimentally measure the effects of all amino-acid point mutations to proteins using deep mutational scanning. These experimental measurements can inform site-specific phylogenetic substitution models of gene evolution in nature. Here we describe software that efficiently performs analyses with such substitution models. This software, phydms, can be used to compare the results of deep mutational scanning experiments to the selection on genes in nature. Given a phylogenetic tree topology inferred with another program, phydms enables rigorous comparison of how well different experiments on the same gene capture actual natural selection. It also enables re-scaling of deep mutational scanning data to account for differences in the stringency of selection in the lab and nature. Finally, phydms can identify sites that are evolving differently in nature than expected from experiments in the lab. As data from deep mutational scanning experiments become increasingly widespread, phydms will facilitate quantitative comparison of the experimental results to the actual selection pressures shaping evolution in nature.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2017_xue.html b/papers/2017_xue.html index c117130..4fcffd3 100644 --- a/papers/2017_xue.html +++ b/papers/2017_xue.html @@ -6,19 +6,19 @@ Parallel evolution of influenza across multiple spatiotemporal scales | Bloom Lab - + - - - - + + + +
eLifeJune 27, 2017

Parallel evolution of influenza across multiple spatiotemporal scales

Katherine S Xue, Terry Stevens-Ayers, Angela P Campbell, Janet A Englund, Steven A Pergam, Michael Boeckh, Jesse D Bloom
doi:10.7554/eLife.26875.001

Abstract ​

Viral variants that arise in the global influenza population begin as de novo mutations in single infected hosts, but the evolutionary dynamics that transform within-host variation to global genetic diversity are poorly understood. Here, we demonstrate that influenza evolution within infected humans recapitulates many evolutionary dynamics observed at the global scale. We deep-sequence longitudinal samples from four immunocompromised patients with long-term H3N2 influenza infections. We find parallel evolution across three scales: within individual patients, in different patients in our study, and in the global influenza population. In hemagglutinin, a small set of mutations arises independently in multiple patients. These same mutations emerge repeatedly within single patients and compete with one another, providing a vivid clinical example of clonal interference. Many of these recurrent within-host mutations also reach a high global frequency in the decade following the patient infections. Our results demonstrate surprising concordance in evolutionary dynamics across multiple spatiotemporal scales.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2018_dingens.html b/papers/2018_dingens.html index c7b4394..a676ee5 100644 --- a/papers/2018_dingens.html +++ b/papers/2018_dingens.html @@ -6,19 +6,19 @@ Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV | Bloom Lab - + - - - - + + + +
PLoS pathogensJuly 5, 2018

Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV

Adam S Dingens, Priyamvada Acharya, Hugh K Haddox, Reda Rawi, Kai Xu, Gwo-Yu Chuang, Hui Wei, Baoshan Zhang, John R Mascola, Bridget Carragher, Clinton S Potter, Julie Overbaugh, Peter D Kwong, Jesse D Bloom
doi:10.1371/journal.ppat.1007159

Abstract ​

Eliciting broadly neutralizing antibodies (bnAbs) targeting envelope (Env) is a major goal of HIV vaccine development, but cross-clade breadth from immunization has only sporadically been observed. Recently, Xu et al (2018) elicited cross-reactive neutralizing antibody responses in a variety of animal models using immunogens based on the epitope of bnAb VRC34.01. The VRC34.01 antibody, which was elicited by natural human infection, targets the N terminus of the Env fusion peptide, a critical component of the virus entry machinery. Here we precisely characterize the functional epitopes of VRC34.01 and two vaccine-elicited murine antibodies by mapping all single amino-acid mutations to the BG505 Env that affect viral neutralization. While escape from VRC34.01 occurred via mutations in both fusion peptide and distal interacting sites of the Env trimer, escape from the vaccine-elicited antibodies was mediated predominantly by mutations in the fusion peptide. Cryo-electron microscopy of four vaccine-elicited antibodies in complex with Env trimer revealed focused recognition of the fusion peptide and provided a structural basis for development of neutralization breadth. Together, these functional and structural data suggest that the breadth of vaccine-elicited antibodies targeting the fusion peptide can be enhanced by specific interactions with additional portions of Env. Thus, our complete maps of viral escape both delineate pathways of resistance to these fusion peptide-directed antibodies and provide a strategy to improve the breadth or potency of future vaccine-induced antibodies against Env’s fusion peptide.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2018_doud.html b/papers/2018_doud.html index 8ffb503..5c902dc 100644 --- a/papers/2018_doud.html +++ b/papers/2018_doud.html @@ -6,19 +6,19 @@ How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin | Bloom Lab - + - - - - + + + +
Nature communicationsApril 11, 2018

How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin

Michael B Doud*, Juhye M Lee*, Jesse D Bloom
doi:10.1038/s41467-018-03665-3

Abstract ​

Influenza virus can escape most antibodies with single mutations. However, rare antibodies broadly neutralize many viral strains. It is unclear how easily influenza virus might escape such antibodies if there was strong pressure to do so. Here, we map all single amino-acid mutations that increase resistance to broad antibodies to H1 hemagglutinin. Our approach not only identifies antigenic mutations but also quantifies their effect sizes. All antibodies select mutations, but the effect sizes vary widely. The virus can escape a broad antibody to hemagglutinin’s receptor-binding site the same way it escapes narrow strain-specific antibodies: via single mutations with huge effects. In contrast, broad antibodies to hemagglutinin’s stalk only select mutations with small effects. Therefore, among the antibodies we examine, breadth is an imperfect indicator of the potential for viral escape via single mutations. Antibodies targeting the H1 hemagglutinin stalk are quantifiably harder to escape than the other antibodies tested here.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2018_haddox.html b/papers/2018_haddox.html index 887c195..de25eaa 100644 --- a/papers/2018_haddox.html +++ b/papers/2018_haddox.html @@ -6,19 +6,19 @@ Mapping mutational effects along the evolutionary landscape of HIV envelope | Bloom Lab - + - - - - + + + +
eLifeMarch 28, 2018

Mapping mutational effects along the evolutionary landscape of HIV envelope

Hugh K Haddox*, Adam S Dingens*, Sarah K Hilton, Julie Overbaugh, Jesse D Bloom
doi:10.7554/eLife.34420

Abstract ​

The immediate evolutionary space accessible to HIV is largely determined by how single amino acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here, we quantify the effects on viral growth of all amino acid mutations to two HIV envelope (Env) proteins that differ at > 100 residues. Most mutations similarly affect both Envs, but the amino acid preferences of a minority of sites have clearly shifted. These shifted sites usually prefer a specific amino acid in one Env, but tolerate many amino acids in the other. Surprisingly, shifts are only slightly enriched at sites that have substituted between the Envs—and many occur at residues that do not even contact substitutions. Therefore, long-range epistasis can unpredictably shift Env’s mutational tolerance during HIV evolution, although the amino acid preferences of most sites are conserved between moderately diverged viral strains.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2018_hilton.html b/papers/2018_hilton.html index 26214f0..32a969b 100644 --- a/papers/2018_hilton.html +++ b/papers/2018_hilton.html @@ -6,19 +6,19 @@ Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence | Bloom Lab - + - - - - + + + +
Virus evolutionJuly 1, 2018

Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence

Sarah K Hilton, Jesse D Bloom
doi:10.1093/ve/vey033

Abstract ​

Molecular phylogenetics is often used to estimate the time since the divergence of modern gene sequences. For highly diverged sequences, such phylogenetic techniques sometimes estimate surprisingly recent divergence times. In the case of viruses, independent evidence indicates that the estimates of deep divergence times from molecular phylogenetics are sometimes too recent. This discrepancy is caused in part by inadequate models of purifying selection leading to branch-length underestimation. Here we examine the effect on branch-length estimation of using models that incorporate experimental measurements of purifying selection. We find that models informed by experimentally measured site-specific amino-acid preferences estimate longer deep branches on phylogenies of influenza virus hemagglutinin. This lengthening of branches is due to more realistic stationary states of the models, and is mostly independent of the branch-length extension from modeling site-to-site variation in amino-acid substitution rate. The branch-length extension from experimentally informed site-specific models is similar to that achieved by other approaches that allow the stationary state to vary across sites. However, the improvements from all of these site-specific but time homogeneous and site independent models are limited by the fact that a protein’s amino-acid preferences gradually shift as it evolves. Overall, our work underscores the importance of modeling site-specific amino-acid preferences when estimating deep divergence times—but also shows the inherent limitations of approaches that fail to account for how these preferences shift over time.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2018_lee.html b/papers/2018_lee.html index bd0a0f9..d52f231 100644 --- a/papers/2018_lee.html +++ b/papers/2018_lee.html @@ -6,19 +6,19 @@ Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants | Bloom Lab - + - - - - + + + +
PNASAugust 28, 2018

Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants

Juhye M Lee, John Huddleston, Michael B Doud, Kathryn A Hooper, Nicholas C Wu, Trevor Bedford, Jesse D Bloom
doi:10.1073/pnas.1806133115

Abstract ​

Human influenza virus rapidly accumulates mutations in its major surface protein hemagglutinin (HA). The evolutionary success of influenza virus lineages depends on how these mutations affect HA’s functionality and antigenicity. Here we experimentally measure the effects on viral growth in cell culture of all single amino acid mutations to the HA from a recent human H3N2 influenza virus strain. We show that mutations that are measured to be more favorable for viral growth are enriched in evolutionarily successful H3N2 viral lineages relative to mutations that are measured to be less favorable for viral growth. Therefore, despite the well-known caveats about cell-culture measurements of viral fitness, such measurements can still be informative for understanding evolution in nature. We also compare our measurements for H3 HA to similar data previously generated for a distantly related H1 HA and find substantial differences in which amino acids are preferred at many sites. For instance, the H3 HA has less disparity in mutational tolerance between the head and stalk domains than the H1 HA. Overall, our work suggests that experimental measurements of mutational effects can be leveraged to help understand the evolutionary fates of viral lineages in nature—but only when the measurements are made on a viral strain similar to the ones being studied in nature.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2018_russell.html b/papers/2018_russell.html index 0b2adf9..2d02104 100644 --- a/papers/2018_russell.html +++ b/papers/2018_russell.html @@ -6,19 +6,19 @@ Extreme heterogeneity of influenza virus infection in single cells | Bloom Lab - + - - - - + + + +
eLifeFebruary 16, 2018

Extreme heterogeneity of influenza virus infection in single cells

Alistair B Russell, Cole Trapnell, Jesse D Bloom
doi:10.7554/eLife.32303

Abstract ​

Viral infection can dramatically alter a cell’s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in the productivity of viral transcription – viral transcripts comprise less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, but this gene absence only partially explains variation in viral transcriptional load. Despite variation in viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2018_xue_a.html b/papers/2018_xue_a.html index 014e2c8..253245b 100644 --- a/papers/2018_xue_a.html +++ b/papers/2018_xue_a.html @@ -6,19 +6,19 @@ Within-host evolution of human influenza virus | Bloom Lab - + - - - - + + + +
Trends in MicrobiologySeptember 1, 2018

Within-host evolution of human influenza virus

Katherine S Xue, Louise H Moncla, Trevor Bedford, Jesse D Bloom
doi:10.1016/j.tim.2018.02.007

Abstract ​

The rapid global evolution of influenza virus begins with mutations that arise de novo in individual infections, but little is known about how evolution occurs within hosts. We review recent progress in understanding how and why influenza viruses evolve within human hosts. Advances in deep sequencing make it possible to measure within-host genetic diversity in both acute and chronic influenza infections. Factors like antigenic selection, antiviral treatment, tissue specificity, spatial structure, and multiplicity of infection may affect how influenza viruses evolve within human hosts. Studies of within-host evolution can contribute to our understanding of the evolutionary and epidemiological factors that shape influenza virus's global evolution.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2018_xue_b.html b/papers/2018_xue_b.html index 8ebb413..b35b387 100644 --- a/papers/2018_xue_b.html +++ b/papers/2018_xue_b.html @@ -6,19 +6,19 @@ Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples | Bloom Lab - + - - - - + + + +
MSphereFebruary 28, 2018

Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples

Katherine S Xue, Alexander L Greninger, Ailyn Pérez-Osorio, Jesse D Bloom
doi:10.1128/mspheredirect.00552-17

Abstract ​

The high mutation rates of RNA viruses lead to rapid genetic diversification, which can enable cooperative interactions between variants in a viral population. We previously described two distinct variants of H3N2 influenza virus that cooperate in cell culture. These variants differ by a single mutation, D151G, in the neuraminidase protein. The D151G mutation reaches a stable frequency of about 50% when virus is passaged in cell culture. However, it is unclear whether selection for the cooperative benefits of D151G is a cell culture phenomenon or whether the mutation is also sometimes present at appreciable frequency in virus populations sampled directly from infected humans. Prior work has not detected D151G in unpassaged clinical samples, but those studies have used methods like Sanger sequencing and pyrosequencing, which are relatively insensitive to low-frequency variation. We identified nine samples of human H3N2 influenza virus collected between 2013 and 2015 in which Sanger sequencing had detected a high frequency of the D151G mutation following one to three passages in cell culture. We deep sequenced the unpassaged clinical samples to identify low-frequency viral variants. The frequency of D151G did not exceed the frequency of library preparation and sequencing errors in any of the sequenced samples. We conclude that passage in cell culture is primarily responsible for the frequent observations of D151G in recent H3N2 influenza virus strains.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2019_crawford.html b/papers/2019_crawford.html index e51f3e4..7fdfee1 100644 --- a/papers/2019_crawford.html +++ b/papers/2019_crawford.html @@ -6,19 +6,19 @@ alignparse: A Python package for parsing complex features from high-throughput long-read sequencing | Bloom Lab - + - - - - + + + +
JOSSJanuary 23, 2019

alignparse: A Python package for parsing complex features from high-throughput long-read sequencing

Katharine HD Crawford, Jesse D Bloom
doi:10.21105/joss.01915

Abstract ​

Advances in sequencing technology have made it possible to generate large numbers of long, high-accuracy sequencing reads. For instance, the new PacBio Sequel platform can generate hundreds of thousands of high-quality circular consensus sequences in a single run (Hebert et al., 2018; Rhoads & Au, 2015). Good programs exist for aligning these reads for genome assembly (Chaisson & Tesler, 2012; Li, 2018). However, these long reads can also be used for other purposes, such as sequencing PCR amplicons that contain various features of interest. For instance, PacBio circular consensus sequences have been used to identify the mutations in influenza viruses in single cells (Russell et al, 2019), or to link barcodes to gene mutants in deep mutational scanning (Matreyek et al., 2018). For such applications, the alignment of the sequences to the targets may be fairly trivial, but it is not trivial to then parse specific features of interest (such as mutations, unique molecular identifiers, cell barcodes, and flanking sequences) from these alignments.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2019_dingens_a.html b/papers/2019_dingens_a.html index 4c74d9a..6ef7a61 100644 --- a/papers/2019_dingens_a.html +++ b/papers/2019_dingens_a.html @@ -6,19 +6,19 @@ Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide | Bloom Lab - + - - - - + + + +
VirusesMay 15, 2019

Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide

Adam S Dingens, Dana Arenz, Julie Overbaugh, Jesse D Bloom
doi:10.3390/v11050439

Abstract ​

Identifying drug resistance mutations is important for the clinical use of antivirals and can help define both a drug’s mechanism of action and the mechanistic basis of resistance. Resistance mutations are often identified one-at-a-time by studying viral evolution within treated patients or during viral growth in the presence of a drug in cell culture. Such approaches have previously mapped resistance to enfuvirtide, the only clinically approved HIV-1 fusion inhibitor, to enfuvirtide’s binding site in the N-terminal heptad repeat (NHR) of the Envelope (Env) transmembrane domain as well as a limited number of allosteric sites. Here, we sought to better delineate the genotypic determinants of resistance throughout Env. We used deep mutational scanning to quantify the effect of all single-amino-acid mutations to the subtype A BG505 Env on resistance to enfuvirtide. We identified both previously characterized and numerous novel resistance mutations in the NHR. Additional resistance mutations clustered in other regions of Env conformational intermediates, suggesting they may act during different fusion steps by altering fusion kinetics and/or exposure of the enfuvirtide binding site. This complete map of resistance sheds light on the diverse mechanisms of enfuvirtide resistance and highlights the utility of using deep mutational scanning to comprehensively map potential drug resistance mutations.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2019_dingens_b.html b/papers/2019_dingens_b.html index c4b0eb6..682607a 100644 --- a/papers/2019_dingens_b.html +++ b/papers/2019_dingens_b.html @@ -6,19 +6,19 @@ An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes | Bloom Lab - + - - - - + + + +
ImmunityFebruary 19, 2019

An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes

Adam S Dingens, Dana Arenz, Haidyn Weight, Julie Overbaugh, Jesse D Bloom
doi:10.1016/j.immuni.2018.12.017

Abstract ​

Anti-HIV broadly neutralizing antibodies (bnAbs) have revealed vaccine targets on the virus’s envelope (Env) protein and are themselves promising immunotherapies. The efficacy of bnAb-based therapies and vaccines depends in part on how readily the virus can escape neutralization. Although structural studies can define contacts between bnAbs and Env, only functional studies can define mutations that confer escape. Here, we mapped how all possible single amino acid mutations in Env affect neutralization of HIV by nine bnAbs targeting five epitopes. For most bnAbs, mutations at only a small fraction of structurally defined contact sites mediated escape, and most escape occurred at sites near, but not in direct contact with, the antibody. The Env mutations selected by two pooled bnAbs were similar to those expected from the combination of the bnAbs’s independent action. Overall, our mutation-level antigenic atlas provides a comprehensive dataset for understanding viral immune escape and refining therapies and vaccines.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2019_lee.html b/papers/2019_lee.html index f75da68..057d1d0 100644 --- a/papers/2019_lee.html +++ b/papers/2019_lee.html @@ -6,19 +6,19 @@ Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin | Bloom Lab - + - - - - + + + +
eLifeAugust 27, 2019

Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin

Juhye M Lee, Rachel Eguia, Seth J Zost, Saket Choudhary, Patrick C Wilson, Trevor Bedford, Terry Stevens-Ayers, Michael Boeckh, Aeron C Hurt, Seema S Lakdawala, Scott E Hensley, Jesse D Bloom
doi:10.7554/eLife.49324

Abstract ​

A longstanding question is how influenza virus evolves to escape human immunity, which is polyclonal and can target many distinct epitopes. Here, we map how all amino-acid mutations to influenza’s major surface protein affect viral neutralization by polyclonal human sera. The serum of some individuals is so focused that it selects single mutations that reduce viral neutralization by over an order of magnitude. However, different viral mutations escape the sera of different individuals. This individual-to-individual variation in viral escape mutations is not present among ferrets that have been infected just once with a defined viral strain. Our results show how different single mutations help influenza virus escape the immunity of different members of the human population, a phenomenon that could shape viral evolution and disease susceptibility.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2019_machkovech.html b/papers/2019_machkovech.html index d04e03e..108905b 100644 --- a/papers/2019_machkovech.html +++ b/papers/2019_machkovech.html @@ -6,19 +6,19 @@ Comprehensive profiling of translation initiation in influenza virus infected cells | Bloom Lab - + - - - - + + + +
PLoS pathogensJanuary 23, 2019

Comprehensive profiling of translation initiation in influenza virus infected cells

Heather M Machkovech, Jesse D Bloom, Arvind R Subramaniam
doi:10.1371/journal.ppat.1007518

Abstract ​

Translation can initiate at alternate, non-canonical start codons in response to stressful stimuli in mammalian cells. Recent studies suggest that viral infection and anti-viral responses alter sites of translation initiation, and in some cases, lead to production of novel immune epitopes. Here we systematically investigate the extent and impact of alternate translation initiation in cells infected with influenza virus. We perform evolutionary analyses that suggest selection against non-canonical initiation at CUG codons in influenza virus lineages that have adapted to mammalian hosts. We then use ribosome profiling with the initiation inhibitor lactimidomycin to experimentally delineate translation initiation sites in a human lung epithelial cell line infected with influenza virus. We identify several candidate sites of alternate initiation in influenza mRNAs, all of which occur at AUG codons that are downstream of canonical initiation codons. One of these candidate downstream start sites truncates 14 amino acids from the N-terminus of the N1 neuraminidase protein, resulting in loss of its cytoplasmic tail and a portion of the transmembrane domain. This truncated neuraminidase protein is expressed on the cell surface during influenza virus infection, is enzymatically active, and is conserved in most N1 viral lineages. We do not detect globally higher levels of alternate translation initiation on host transcripts upon influenza infection or during the anti-viral response, but the subset of host transcripts induced by the anti-viral response is enriched for alternate initiation sites. Together, our results systematically map the landscape of translation initiation during influenza virus infection, and shed light on the evolutionary forces shaping this landscape.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2019_russell.html b/papers/2019_russell.html index b7bd0bd..24e8c05 100644 --- a/papers/2019_russell.html +++ b/papers/2019_russell.html @@ -6,19 +6,19 @@ Single-cell virus sequencing of influenza infections that trigger innate immunity | Bloom Lab - + - - - - + + + +
Journal of virologyJuly 15, 2019

Single-cell virus sequencing of influenza infections that trigger innate immunity

Alistair B Russell, Elizaveta Elshina, Jacob R Kowalsky, Aartjan JW Te Velthuis, Jesse D Bloom
doi:10.1128/jvi.00500-19

Abstract ​

Influenza virus-infected cells vary widely in their expression of viral genes and only occasionally activate innate immunity. Here, we develop a new method to assess how the genetic variation in viral populations contributes to this heterogeneity. We do this by determining the transcriptome and full-length sequences of all viral genes in single cells infected with a nominally “pure” stock of influenza virus. Most cells are infected by virions with defects, some of which increase the frequency of innate-immune activation. These immunostimulatory defects are diverse and include mutations that perturb the function of the viral polymerase protein PB1, large internal deletions in viral genes, and failure to express the virus’s interferon antagonist NS1. However, immune activation remains stochastic in cells infected by virions with these defects and occasionally is triggered even by virions that express unmutated copies of all genes. Our work shows that the diverse spectrum of defects in influenza virus populations contributes to—but does not completely explain—the heterogeneity in viral gene expression and immune activation in single infected cells.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2019_soh.html b/papers/2019_soh.html index 8a1a99a..ac1a18f 100644 --- a/papers/2019_soh.html +++ b/papers/2019_soh.html @@ -6,19 +6,19 @@ Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans | Bloom Lab - + - - - - + + + +
eLifeApril 30, 2019

Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans

YQ Shirleen Soh, Louise H Moncla, Rachel Eguia, Trevor Bedford, Jesse D Bloom
doi:10.7554/eLife.45079

Abstract ​

Viruses like influenza are infamous for their ability to adapt to new hosts. Retrospective studies of natural zoonoses and passaging in the lab have identified a modest number of host-adaptive mutations. However, it is unclear if these mutations represent all ways that influenza can adapt to a new host. Here we take a prospective approach to this question by completely mapping amino-acid mutations to the avian influenza virus polymerase protein PB2 that enhance growth in human cells. We identify numerous previously uncharacterized human-adaptive mutations. These mutations cluster on PB2’s surface, highlighting potential interfaces with host factors. Some previously uncharacterized adaptive mutations occur in avian-to-human transmission of H7N9 influenza, showing their importance for natural virus evolution. But other adaptive mutations do not occur in nature because they are inaccessible via single-nucleotide mutations. Overall, our work shows how selection at key molecular surfaces combines with evolutionary accessibility to shape viral host adaptation.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2019_xue_a.html b/papers/2019_xue_a.html index 635c732..bfc19fc 100644 --- a/papers/2019_xue_a.html +++ b/papers/2019_xue_a.html @@ -6,19 +6,19 @@ Reconciling disparate estimates of viral genetic diversity during human influenza infections | Bloom Lab - + - - - - + + + +
Nature geneticsSeptember 1, 2019

Reconciling disparate estimates of viral genetic diversity during human influenza infections

Katherine S Xue, Jesse D Bloom
doi:10.1038/s41588-019-0349-3

Abstract ​

To the Editor — A key question in the study of influenza virus evolution is how rapidly viral genetic variation arises within infected humans1,2. Recently, several studies have measured influenza’s within-host genetic diversity in large cohorts of infected humans through high-throughput deep sequencing3,4,5,6 (Supplementary Table 1). These studies disagree in their estimates of influenza’s within-host genetic diversity. In a Nature Genetics letter titled ‘Quantifying influenza virus diversity and transmission in humans’, analyzing a household cohort in Hong Kong, Poon et al.4 have estimated that within-host genetic diversity is high, and 200–250 viral genomes are transmitted between individuals. However, several recent studies conducted in Wisconsin3, Michigan6, and Washington7 that used similar methodologies have estimated lower levels of viral genetic diversity. In particular, the Michigan study has estimated a narrow transmission bottleneck of just one or two viral genomes6. We sought to examine whether technical differences in the underlying deep-sequencing datasets or the methods used to analyze them might explain the disparate estimates of within-host viral genetic diversity. We identified an anomaly in the Hong Kong data that provides a technical explanation for these discrepancies: read pairs from this study are often split between different biological samples, thus indicating that some reads are incorrectly assigned.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2020_crawford.html b/papers/2020_crawford.html index 7df0d15..1b4b2cc 100644 --- a/papers/2020_crawford.html +++ b/papers/2020_crawford.html @@ -6,19 +6,19 @@ Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays | Bloom Lab - + - - - - + + + +
VirusesMay 6, 2020

Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays

Katharine HD Crawford, Rachel Eguia, Adam S Dingens, Andrea N Loes, Keara D Malone, Caitlin R Wolf, Helen Y Chu, M Alejandra Tortorici, David Veesler, Michael Murphy, Deleah Pettie, Neil P King, Alejandro B Balazs, Jesse D Bloom
doi:10.3390/v12050513

Abstract ​

SARS-CoV-2 enters cells using its Spike protein, which is also the main target of neutralizing antibodies. Therefore, assays to measure how antibodies and sera affect Spike-mediated viral infection are important for studying immunity. Because SARS-CoV-2 is a biosafety-level-3 virus, one way to simplify such assays is to pseudotype biosafety-level-2 viral particles with Spike. Such pseudotyping has now been described for single-cycle lentiviral, retroviral, and vesicular stomatitis virus (VSV) particles, but the reagents and protocols are not widely available. Here, we detailed how to effectively pseudotype lentiviral particles with SARS-CoV-2 Spike and infect 293T cells engineered to express the SARS-CoV-2 receptor, ACE2. We also made all the key experimental reagents available in the BEI Resources repository of ATCC and the NIH. Furthermore, we demonstrated how these pseudotyped lentiviral particles could be used to measure the neutralizing activity of human sera or plasma against SARS-CoV-2 in convenient luciferase-based assays, thereby providing a valuable complement to ELISA-based methods that measure antibody binding rather than neutralization.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2020_dingens.html b/papers/2020_dingens.html index 557f5a2..dfdd449 100644 --- a/papers/2020_dingens.html +++ b/papers/2020_dingens.html @@ -6,19 +6,19 @@ Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak | Bloom Lab - + - - - - + + + +
Nature communicationsSeptember 1, 2020

Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak

Adam S Dingens, Katharine HD Crawford, Amanda Adler, Sarah L Steele, Kirsten Lacombe, Rachel Eguia, Fatima Amanat, Alexandra C Walls, Caitlin R Wolf, Michael Murphy, Deleah Pettie, Lauren Carter, Xuan Qin, Neil P King, David Veesler, Florian Krammer, Jane A Dickerson, Helen Y Chu, Janet A Englund, Jesse D Bloom
doi:10.1038/s41467-020-18178-1

Abstract ​

Children are strikingly underrepresented in COVID-19 case counts. In the United States, children represent 22% of the population but only 1.7% of confirmed SARS-CoV-2 cases as of April 2, 2020. One possibility is that symptom-based viral testing is less likely to identify infected children, since they often experience milder disease than adults. Here, to better assess the frequency of pediatric SARS-CoV-2 infection, we serologically screen 1,775 residual samples from Seattle Children’s Hospital collected from 1,076 children seeking medical care during March and April of 2020. Only one child was seropositive in March, but seven were seropositive in April for a period seroprevalence of ≈1%. Most seropositive children (6/8) were not suspected of having had COVID-19. The sera of seropositive children have neutralizing activity, including one that neutralized at a dilution > 1:18,000. Therefore, an increasing number of children seeking medical care were infected by SARS-CoV-2 during the early Seattle outbreak despite few positive viral tests.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2020_einav_b.html b/papers/2020_einav_b.html index 3d2b444..a2c0436 100644 --- a/papers/2020_einav_b.html +++ b/papers/2020_einav_b.html @@ -6,19 +6,19 @@ When two are better than one: Modeling the mechanisms of antibody mixtures | Bloom Lab - + - - - - + + + +
PLoS computational biologyMay 4, 2020

When two are better than one: Modeling the mechanisms of antibody mixtures

Tal Einav, Jesse D Bloom
doi:10.1371/journal.pcbi.1007830

Abstract ​

It is difficult to predict how antibodies will behave when mixed together, even after each has been independently characterized. Here, we present a statistical mechanical model for the activity of antibody mixtures that accounts for whether pairs of antibodies bind to distinct or overlapping epitopes. This model requires measuring n individual antibodies and their pairwise interactions to predict the 2n potential combinations. We apply this model to epidermal growth factor receptor (EGFR) antibodies and find that the activity of antibody mixtures can be predicted without positing synergy at the molecular level. In addition, we demonstrate how the model can be used in reverse, where straightforward experiments measuring the activity of antibody mixtures can be used to infer the molecular interactions between antibodies. Lastly, we generalize this model to analyze engineered multidomain antibodies, where components of different antibodies are tethered together to form novel amalgams, and characterize how well it predicts recently designed influenza antibodies.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2020_gentles.html b/papers/2020_gentles.html index 6240a71..413663c 100644 --- a/papers/2020_gentles.html +++ b/papers/2020_gentles.html @@ -6,19 +6,19 @@ Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding | Bloom Lab - + - - - - + + + +
VirusesMay 30, 2020

Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding

Lauren E Gentles, Hongquan Wan, Maryna C Eichelberger, Jesse D Bloom
doi:10.3390/v12060597

Abstract ​

Influenza virus infection elicits antibodies against the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Because HA is essential for viral entry, antibodies targeting HA often potently neutralize the virus in single-cycle infection assays. However, antibodies against NA are not potently neutralizing in such assays, since NA is dispensable for single-cycle infection. Here we show that a modified influenza virus that depends on NA for receptor binding is much more sensitive than a virus with receptor-binding HA to neutralization by some anti-NA antibodies. Specifically, a virus with a receptor-binding G147R N1 NA and a binding-deficient HA is completely neutralized in single-cycle infections by an antibody that binds near the NA active site. Infection is also substantially inhibited by antibodies that bind NA epitopes distant from the active site. Finally, we demonstrate that this modified virus can be used to efficiently select mutations in NA that escape antibody binding, a task that can be laborious with typical influenza viruses that are not well neutralized by anti-NA antibodies. Thus, viruses dependent on NA for receptor binding allow for sensitive in vitro detection of antibodies binding near the catalytic site of NA and enable the selection of viral escape mutants.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2020_hilton.html b/papers/2020_hilton.html index 52676f7..84db971 100644 --- a/papers/2020_hilton.html +++ b/papers/2020_hilton.html @@ -6,19 +6,19 @@ dms-view: Interactive visualization tool for deep mutational scanning data | Bloom Lab - + - - - - + + + +
JOSSAugust 17, 2020

dms-view: Interactive visualization tool for deep mutational scanning data

Sarah K Hilton*, John Huddleston*, Allison Black, Khrystyna North, Adam S Dingens, Trevor Bedford, Jesse D Bloom
doi:10.21105/joss.02353

Abstract ​

Here we describe dms-view (https://dms-view.github.io/), a flexible, web-based, interactive visualization tool for DMS data.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2020_loes.html b/papers/2020_loes.html index 6770617..ca54c6c 100644 --- a/papers/2020_loes.html +++ b/papers/2020_loes.html @@ -6,19 +6,19 @@ Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice | Bloom Lab - + - - - - + + + +
VirusesSeptember 5, 2020

Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice

Andrea N Loes, Lauren E Gentles, Allison J Greaney, Katharine HD Crawford, Jesse D Bloom
doi:10.3390/v12090987

Abstract ​

An effective vaccine is essential for controlling the spread of the SARS-CoV-2 virus. Here, we describe an influenza virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ΔNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ΔNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (~1:200). Furthermore, ΔNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ΔNA(RBD)-Flu at scale by leveraging existing platforms for the production of influenza vaccines.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2020_roop.html b/papers/2020_roop.html index 1275a9c..39adf5a 100644 --- a/papers/2020_roop.html +++ b/papers/2020_roop.html @@ -6,19 +6,19 @@ Identification of HIV-1 envelope mutations that enhance entry using macaque CD4 and CCR5 | Bloom Lab - + - - - - + + + +
VirusesFebruary 21, 2020

Identification of HIV-1 envelope mutations that enhance entry using macaque CD4 and CCR5

Jeremy I Roop, Noah A Cassidy, Adam S Dingens, Jesse D Bloom, Julie Overbaugh
doi:10.3390/v12020241

Abstract ​

Although Rhesus macaques are an important animal model for HIV-1 vaccine development research, most transmitted HIV-1 strains replicate poorly in macaque cells. A major genetic determinant of this species-specific restriction is a non-synonymous mutation in macaque CD4 that results in reduced HIV-1 Envelope (Env)-mediated viral entry compared to human CD4. Recent research efforts employing either laboratory evolution or structure-guided design strategies have uncovered several mutations in Env’s gp120 subunit that enhance binding of macaque CD4 by transmitted/founder HIV-1 viruses. In order to identify additional Env mutations that promote infection of macaque cells, we utilized deep mutational scanning to screen thousands of Env point mutants for those that enhance HIV-1 entry via macaque receptors. We identified many uncharacterized amino acid mutations in the N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR) regions of gp41 that increased entry into cells bearing macaque receptors up to 9-fold. Many of these mutations also modestly increased infection of cells bearing human CD4 and CCR5 (up to 1.5-fold). NHR/CHR mutations identified by deep mutational scanning that enhanced entry also increased sensitivity to neutralizing antibodies targeting the MPER epitope, and to inactivation by cold-incubation, suggesting that they promote sampling of an intermediate trimer conformation between closed and receptor bound states. Identification of this set of mutations can inform future macaque model studies, and also further our understanding of the relationship between Env structure and function.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2020_starr_a.html b/papers/2020_starr_a.html index ee4da35..61d5da9 100644 --- a/papers/2020_starr_a.html +++ b/papers/2020_starr_a.html @@ -6,19 +6,19 @@ Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding | Bloom Lab - + - - - - + + + +
CellSeptember 3, 2020

Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding

Tyler N Starr*, Allison J Greaney*, Sarah K Hilton, Daniel Ellis, Katharine HD Crawford, Adam S Dingens, Mary Jane Navarro, John E Bowen, Alejandra M Tortorici, Alexandra C Walls, Neil P King, David Veesler, Jesse D Bloom
doi:10.1016/j.cell.2020.08.012

Abstract ​

The receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein mediates viral attachment to ACE2 receptor and is a major determinant of host range and a dominant target of neutralizing antibodies. Here, we experimentally measure how all amino acid mutations to the RBD affect expression of folded protein and its affinity for ACE2. Most mutations are deleterious for RBD expression and ACE2 binding, and we identify constrained regions on the RBD’s surface that may be desirable targets for vaccines and antibody-based therapeutics. But a substantial number of mutations are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses. However, we find no evidence that these ACE2-affinity-enhancing mutations have been selected in current SARS-CoV-2 pandemic isolates. We present an interactive visualization and open analysis pipeline to facilitate use of our dataset for vaccine design and functional annotation of mutations observed during viral surveillance.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2020_xue.html b/papers/2020_xue.html index 5db35e6..89f6817 100644 --- a/papers/2020_xue.html +++ b/papers/2020_xue.html @@ -6,19 +6,19 @@ Linking influenza virus evolution within and between human hosts | Bloom Lab - + - - - - + + + +
Virus evolutionJanuary 1, 2020

Linking influenza virus evolution within and between human hosts

Katherine S Xue, Jesse D Bloom
doi:10.1093/ve/veaa010

Abstract ​

Influenza viruses rapidly diversify within individual human infections. Several recent studies have deep-sequenced clinical influenza infections to identify viral variation within hosts, but it remains unclear how within-host mutations fare at the between-host scale. Here, we compare the genetic variation of H3N2 influenza within and between hosts to link viral evolutionary dynamics across scales. Synonymous sites evolve at similar rates at both scales, indicating that global evolution at these putatively neutral sites results from the accumulation of within-host variation. However, nonsynonymous mutations are depleted between hosts compared to within hosts, suggesting that selection purges many of the protein-altering changes that arise within hosts. The exception is at antigenic sites, where selection detectably favors nonsynonymous mutations at the global scale, but not within hosts. These results suggest that selection against deleterious mutations and selection for antigenic change are the main forces that act on within-host variants of influenza virus as they transmit and circulate between hosts.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2021_bloom_a.html b/papers/2021_bloom_a.html index 9dfba1b..16a1da8 100644 --- a/papers/2021_bloom_a.html +++ b/papers/2021_bloom_a.html @@ -6,19 +6,19 @@ Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic | Bloom Lab - + - - - - + + + +
mBioDecember 1, 2021

Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic

Jesse D Bloom
doi:10.1093/molbev/msab246

Abstract ​

The origin and early spread of SARS-CoV-2 remains shrouded in mystery. Here, I identify a data set containing SARS-CoV-2 sequences from early in the Wuhan epidemic that has been deleted from the NIH’s Sequence Read Archive. I recover the deleted files from the Google Cloud and reconstruct partial sequences of 13 early epidemic viruses. Phylogenetic analysis of these sequences in the context of carefully annotated existing data further supports the idea that the Huanan Seafood Market sequences are not fully representative of the viruses in Wuhan early in the epidemic. Instead, the progenitor of currently known SARS-CoV-2 sequences likely contained three mutations relative to the market viruses that made it more similar to SARS-CoV-2’s bat coronavirus relatives.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2021_crawford.html b/papers/2021_crawford.html index 8faae90..2499556 100644 --- a/papers/2021_crawford.html +++ b/papers/2021_crawford.html @@ -6,19 +6,19 @@ Dynamics of neutralizing antibody titers in the months after severe acute respiratory syndrome coronavirus 2 infection | Bloom Lab - + - - - - + + + +
The Journal of infectious diseasesJanuary 15, 2021

Dynamics of neutralizing antibody titers in the months after severe acute respiratory syndrome coronavirus 2 infection

Katharine HD Crawford, Adam S Dingens, Rachel Eguia, Caitlin R Wolf, Naomi Wilcox, Jennifer K Logue, Kiel Shuey, Amanda M Casto, Brooke Fiala, Samuel Wrenn, Deleah Pettie, Neil P King, Alexander L Greninger, Helen Y Chu, Jesse D Bloom
doi:10.1093/infdis/jiaa618

Abstract ​

Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop neutralizing antibodies that target the viral spike protein. In this study, we quantified how levels of these antibodies change in the months after SARS-CoV-2 infection by examining longitudinal samples collected approximately 30–152 days after symptom onset from a prospective cohort of 32 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about 4-fold from 1 to 4 months after symptom onset. This decline in neutralizing antibody titers was accompanied by a decline in total antibodies capable of binding the viral spike protein or its receptor-binding domain. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2021_dingens.html b/papers/2021_dingens.html index b2c9c77..d1b1dd0 100644 --- a/papers/2021_dingens.html +++ b/papers/2021_dingens.html @@ -6,19 +6,19 @@ High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination | Bloom Lab - + - - - - + + + +
eLifeJanuary 13, 2021

High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination

Adam S Dingens, Payal Pratap, Keara Malone, Sarah K Hilton, Thomas Ketas, Christopher A Cottrell, Julie Overbaugh, John P Moore, PJ Klasse, Andrew B Ward, Jesse D Bloom
doi:10.7554/eLife.64281

Abstract ​

Mapping polyclonal serum responses is critical to rational vaccine design. However, most high-resolution mapping approaches involve isolating and characterizing individual antibodies, which incompletely defines the polyclonal response. Here we use two complementary approaches to directly map the specificities of the neutralizing and binding antibodies of polyclonal anti-HIV-1 sera from rabbits immunized with BG505 Env SOSIP trimers. We used mutational antigenic profiling to determine how all mutations in Env affected viral neutralization and electron microscopy polyclonal epitope mapping (EMPEM) to directly visualize serum Fabs bound to Env trimers. The dominant neutralizing specificities were generally only a subset of the more diverse binding specificities. Additional differences between binding and neutralization reflected antigenicity differences between virus and soluble Env trimer. Furthermore, we refined residue-level epitope specificity directly from sera, revealing subtle differences across sera. Together, mutational antigenic profiling and EMPEM yield a holistic view of the binding and neutralizing specificity of polyclonal sera.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2021_eguia.html b/papers/2021_eguia.html index e652e53..71c2eab 100644 --- a/papers/2021_eguia.html +++ b/papers/2021_eguia.html @@ -6,19 +6,19 @@ A human coronavirus evolves antigenically to escape antibody immunity | Bloom Lab - + - - - - + + + +
PLoS pathogensApril 8, 2021

A human coronavirus evolves antigenically to escape antibody immunity

Rachel T Eguia, Katharine HD Crawford, Terry Stevens-Ayers, Laurel Kelnhofer-Millevolte, Alexander L Greninger, Janet A Englund, Michael J Boeckh, Jesse D Bloom
doi:10.1371/journal.ppat.1009453

Abstract ​

There is intense interest in antibody immunity to coronaviruses. However, it is unknown if coronaviruses evolve to escape such immunity, and if so, how rapidly. Here we address this question by characterizing the historical evolution of human coronavirus 229E. We identify human sera from the 1980s and 1990s that have neutralizing titers against contemporaneous 229E that are comparable to the anti-SARS-CoV-2 titers induced by SARS-CoV-2 infection or vaccination. We test these sera against 229E strains isolated after sera collection, and find that neutralizing titers are lower against these “future” viruses. In some cases, sera that neutralize contemporaneous 229E viral strains with titers >1:100 do not detectably neutralize strains isolated 8–17 years later. The decreased neutralization of “future” viruses is due to antigenic evolution of the viral spike, especially in the receptor-binding domain. If these results extrapolate to other coronaviruses, then it may be advisable to periodically update SARS-CoV-2 vaccines.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2021_greaney_a.html b/papers/2021_greaney_a.html index 41d3358..3c771c2 100644 --- a/papers/2021_greaney_a.html +++ b/papers/2021_greaney_a.html @@ -6,19 +6,19 @@ Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies | Bloom Lab - + - - - - + + + +
Nature CommunicationsJuly 7, 2021

Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies

Allison J Greaney, Tyler N Starr, Christopher O Barnes, Yiska Weisblum, Fabian Schmidt, Marina Caskey, Christian Gaebler, Alice Cho, Marianna Agudelo, Shlomo Finkin, Zijun Wang, Daniel Poston, Frauke Muecksch, Theodora Hatziioannou, Paul D Bieniasz, Davide F Robbiani, Michel C Nussenzweig, Pamela J Bjorkman, Jesse D Bloom
doi:10.1038/s41467-021-24435-8

Abstract ​

Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasmas, including plasmas from individuals from whom some of the antibodies were isolated. While the binding of polyclonal plasma antibodies are affected by mutations across multiple RBD epitopes, the plasma-escape maps most resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is skewed towards a single class of antibodies targeting an epitope that is already undergoing rapid evolution.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2021_greaney_b.html b/papers/2021_greaney_b.html index be47fcd..5477772 100644 --- a/papers/2021_greaney_b.html +++ b/papers/2021_greaney_b.html @@ -6,19 +6,19 @@ Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection | Bloom Lab - + - - - - + + + +
Science translational medicineJune 30, 2021

Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection

Allison J Greaney, Andrea N Loes, Lauren E Gentles, Katharine HD Crawford, Tyler N Starr, Keara D Malone, Helen Y Chu, Jesse D Bloom
doi:10.1126/scitranslmed.abi9915

Abstract ​

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with mutations in key antibody epitopes has raised concerns that antigenic evolution could erode adaptive immunity elicited by prior infection or vaccination. The susceptibility of immunity to viral evolution is shaped in part by the breadth of epitopes targeted by antibodies elicited by vaccination or natural infection. To investigate how human antibody responses to vaccines are influenced by viral mutations, we used deep mutational scanning to compare the specificity of polyclonal antibodies elicited by either two doses of the mRNA-1273 COVID-19 vaccine or natural infection with SARS-CoV-2. The neutralizing activity of vaccine-elicited antibodies was more targeted to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein compared to antibodies elicited by natural infection. However, within the RBD, binding of vaccine-elicited antibodies was more broadly distributed across epitopes compared to infection-elicited antibodies. This greater binding breadth means that single RBD mutations have less impact on neutralization by vaccine sera compared to convalescent sera. Therefore, antibody immunity acquired by natural infection or different modes of vaccination may have a differing susceptibility to erosion by SARS-CoV-2 evolution.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2021_greaney_c.html b/papers/2021_greaney_c.html index b3deaf6..548c910 100644 --- a/papers/2021_greaney_c.html +++ b/papers/2021_greaney_c.html @@ -6,19 +6,19 @@ Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies | Bloom Lab - + - - - - + + + +
Cell host & microbeMarch 10, 2021

Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies

Allison J Greaney, Andrea N Loes, Katharine HD Crawford, Tyler N Starr, Keara D Malone, Helen Y Chu, Jesse D Bloom
doi:10.1016/j.chom.2021.02.003

Abstract ​

The evolution of SARS-CoV-2 could impair recognition of the virus by human antibody-mediated immunity. To facilitate prospective surveillance for such evolution, we map how convalescent plasma antibodies are impacted by all mutations to the spike’s receptor-binding domain (RBD), the main target of plasma neutralizing activity. Binding by polyclonal plasma antibodies is affected by mutations in three main epitopes in the RBD, but longitudinal samples reveal that the impact of these mutations on antibody binding varies substantially both among individuals and within the same individual over time. Despite this inter- and intra-person heterogeneity, the mutations that most reduce antibody binding usually occur at just a few sites in the RBD’s receptor-binding motif. The most important site is E484, where neutralization by some plasma is reduced >10-fold by several mutations, including one in the emerging 20H/501Y.V2 and 20J/501Y.V3 SARS-CoV-2 lineages. Going forward, these plasma escape maps can inform surveillance of SARS-CoV-2 evolution.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2021_greaney_d.html b/papers/2021_greaney_d.html index 98236ca..869213c 100644 --- a/papers/2021_greaney_d.html +++ b/papers/2021_greaney_d.html @@ -6,19 +6,19 @@ Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition | Bloom Lab - + - - - - + + + +
Cell host & microbeJanuary 13, 2021

Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition

Allison J Greaney*, Tyler N Starr*, Pavlo Gilchuk, Seth J Zost, Elad Binshtein, Andrea N Loes, Sarah K Hilton, John Huddleston, Rachel Eguia, Katharine HD Crawford, Adam S Dingens, Rachel S Nargi, Rachel E Sutton, Naveenchandra Suryadevara, Paul W Rothlauf, Zhuoming Liu, Sean PJ Whelan, Robert H Carnahan, James E Crowe, Jesse D Bloom
doi:10.1016/j.chom.2020.11.007

Abstract ​

Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies. They further enable the design of escape-resistant antibody cocktails—including cocktails of antibodies that compete for binding to the same RBD surface but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2021_greaney_welsh.html b/papers/2021_greaney_welsh.html index 4662be7..b15c293 100644 --- a/papers/2021_greaney_welsh.html +++ b/papers/2021_greaney_welsh.html @@ -6,19 +6,19 @@ Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution | Bloom Lab - + - - - - + + + +
Cell Reports MedicineApril 20, 2021

Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution

Allison J Greaney, Frances C Welsh, Jesse D Bloom
doi:10.1016/j.xcrm.2021.100257

Abstract ​

Munoz-Alia and colleagues demonstrate that neutralizing antibody immunity to measles resists viral evolutionary escape because it targets numerous distinct viral epitopes. Their work contributes to our understanding of what determines whether a virus can evolve to evade immunity.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2021_soh.html b/papers/2021_soh.html index b1eaaaf..6377fe6 100644 --- a/papers/2021_soh.html +++ b/papers/2021_soh.html @@ -6,19 +6,19 @@ Comprehensive profiling of mutations to influenza virus PB2 that confer resistance to the cap-binding inhibitor pimodivir | Bloom Lab - + - - - - + + + +
VirusesJune 22, 2021

Comprehensive profiling of mutations to influenza virus PB2 that confer resistance to the cap-binding inhibitor pimodivir

Shirleen YQ Soh, Keara D Malone, Rachel T Eguia, Jesse D Bloom
doi:10.3390/v13071196

Abstract ​

Antivirals are used not only in the current treatment of influenza but are also stockpiled as a first line of defense against novel influenza strains for which vaccines have yet to be developed. Identifying drug resistance mutations can guide the clinical deployment of the antiviral and can additionally define the mechanisms of drug action and drug resistance. Pimodivir is a first-in-class inhibitor of the polymerase basic protein 2 (PB2) subunit of the influenza A virus polymerase complex. A number of resistance mutations have previously been identified in treated patients or cell culture. Here, we generate a complete map of the effect of all single-amino-acid mutations to an avian PB2 on resistance to pimodivir. We identified both known and novel resistance mutations not only in the previously implicated cap-binding and mid-link domains, but also in the N-terminal domain. Our complete map of pimodivir resistance thus enables the evaluation of whether new viral strains contain mutations that will confer pimodivir resistance.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2021_starr_b.html b/papers/2021_starr_b.html index f3bf579..d4bbf45 100644 --- a/papers/2021_starr_b.html +++ b/papers/2021_starr_b.html @@ -6,19 +6,19 @@ Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016 | Bloom Lab - + - - - - + + + +
Cell Reports MedicineApril 20, 2021

Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016

Tyler N Starr, Allison J Greaney, Adam S Dingens, Jesse D Bloom
doi:10.1016/j.xcrm.2021.100255

Abstract ​

Monoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for coronavirus disease 2019 (COVID-19). However, ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can render monoclonal antibodies ineffective. Here, we completely map all of the mutations to the SARS-CoV-2 spike receptor-binding domain (RBD) that escape binding by a leading monoclonal antibody, LY-CoV555, and its cocktail combination with LY-CoV016. Individual mutations that escape binding by each antibody are combined in the circulating B.1.351 and P.1 SARS-CoV-2 lineages (E484K escapes LY-CoV555, K417N/T escapes LY-CoV016). In addition, the L452R mutation in the B.1.429 lineage escapes LY-CoV555. Furthermore, we identify single amino acid changes that escape the combined LY-CoV555+LY-CoV016 cocktail. We suggest that future efforts diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to the antigenic evolution of SARS-CoV-2.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2021_starr_greaney.html b/papers/2021_starr_greaney.html index 0fb268e..35d3dba 100644 --- a/papers/2021_starr_greaney.html +++ b/papers/2021_starr_greaney.html @@ -6,19 +6,19 @@ Prospective mapping of viral mutations that escape antibodies used to treat COVID-19 | Bloom Lab - + - - - - + + + +
ScienceFebruary 19, 2021

Prospective mapping of viral mutations that escape antibodies used to treat COVID-19

Tyler N Starr*, Allison J Greaney*, Amin Addetia, William W Hannon, Manish C Choudhary, Adam S Dingens, Jonathan Z Li, Jesse D Bloom
doi:10.1126/science.abf9302

Abstract ​

Antibodies are a potential therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to the receptor binding domain (RBD) of SARS-CoV-2 affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies, REGN10933 and REGN10987, targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2 and during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. These complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2021_starr_greaney_a.html b/papers/2021_starr_greaney_a.html index 6908c5a..0231f8a 100644 --- a/papers/2021_starr_greaney_a.html +++ b/papers/2021_starr_greaney_a.html @@ -6,19 +6,19 @@ SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape | Bloom Lab - + - - - - + + + +
NatureSeptember 2, 2021

SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape

Tyler N Starr, Nadine Czudnochowski, Zhuoming Liu, Fabrizia Zatta, Young-Jun Park, Amin Addetia, Dora Pinto, Martina Beltramello, Patrick Hernandez, Allison J Greaney, Roberta Marzi, William G Glass, Ivy Zhang, Adam S Dingens, John E Bowen, M Alejandra Tortorici, Alexandra C Walls, Jason A Wojcechowskyj, Anna De Marco, Laura E Rosen, Jiayi Zhou, Martin Montiel-Ruiz, Hannah Kaiser, Josh R Dillen, Heather Tucker, Jessica Bassi, Chiara Silacci-Fregni, Michael P Housley, Julia di Iulio, Gloria Lombardo, Maria Agostini, Nicole Sprugasci, Katja Culap, Stefano Jaconi, Marcel Meury, Exequiel Dellota Jr, Rana Abdelnabi, Shi-Yan Caroline Foo, Elisabetta Cameroni, Spencer Stumpf, Tristan I Croll, Jay C Nix, Colin Havenar-Daughton, Luca Piccoli, Fabio Benigni, Johan Neyts, Amalio Telenti, Florian A Lempp, Matteo S Pizzuto, John D Chodera, Christy M Hebner, Herbert W Virgin, Sean PJ Whelan, David Veesler, Davide Corti, Jesse D Bloom, Gyorgy Snell
doi:10.1038/s41586-021-03807-6

Abstract ​

An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape, have activity against diverse sarbecoviruses, and be highly protective through viral neutralization and effector functions. Understanding how these properties relate to each other and vary across epitopes would aid the development of therapeutic antibodies and guide vaccine design. Here we comprehensively characterize escape, breadth and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD). Despite a trade-off between in vitro neutralization potency and breadth of sarbecovirus binding, we identify neutralizing antibodies with exceptional sarbecovirus breadth and a corresponding resistance to SARS-CoV-2 escape. One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a cryptic epitope and prophylactically protects hamsters from viral challenge. Antibodies that target the angiotensin-converting enzyme 2 (ACE2) receptor-binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency. Nevertheless, we also characterize a potent RBM antibody (S2E128) with breadth across sarbecoviruses related to SARS-CoV-2 and a high barrier to viral escape. These data highlight principles underlying variation in escape, breadth and potency among antibodies that target the RBD, and identify epitopes and features to prioritize for therapeutic development against the current and potential future pandemics.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2022_farrell.html b/papers/2022_farrell.html index bc06706..c54ae33 100644 --- a/papers/2022_farrell.html +++ b/papers/2022_farrell.html @@ -6,19 +6,19 @@ Receptor-binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2 | Bloom Lab - + - - - - + + + +
VirusesSeptember 16, 2022

Receptor-binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2

Ariana Ghez Farrell*, Bernadeta Dadonaite*, Allison J Greaney, Rachel Eguia, Andrea N Loes, Nicholas M Franko, Jennifer Logue, Juan Manuel Carreño, Anass Abbad, Helen Y Chu, Kenneth A Matreyek, Jesse D Bloom
doi:10.3390/v14092061

Abstract ​

Neutralization assays are experimental surrogates for the effectiveness of infection- or vaccine-elicited polyclonal antibodies and therapeutic monoclonal antibodies targeting SARS-CoV-2. However, the measured neutralization can depend on the details of the experimental assay. Here, we systematically assess how ACE2 expression in target cells affects neutralization by antibodies to different spike epitopes in lentivirus pseudovirus neutralization assays. For high ACE2-expressing target cells, receptor-binding domain (RBD) antibodies account for nearly all neutralizing activity in polyclonal human sera. However, for lower ACE2-expressing target cells, antibodies targeting regions outside the RBD make a larger (although still modest) contribution to serum neutralization. These serum-level results are mirrored for monoclonal antibodies: N-terminal domain (NTD) antibodies and RBD antibodies that do not compete for ACE2 binding incompletely neutralize on high ACE2-expressing target cells, but completely neutralize on cells with lower ACE2 expression. Our results show that the ACE2 expression level in the target cells is an important experimental variable, and that high ACE2 expression emphasizes the role of a subset of RBD-directed antibodies.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2022_gentles.html b/papers/2022_gentles.html index e6f7352..4eb8b1f 100644 --- a/papers/2022_gentles.html +++ b/papers/2022_gentles.html @@ -6,19 +6,19 @@ Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time | Bloom Lab - + - - - - + + + +
medRxivJanuary 25, 2022

Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time

Lauren E Gentles, Leanne Kehoe, Katharine HD Crawford, Kirsten Lacombe, Jane Dickerson, Caitlin Wolf, Joanna Yuan, Susanna Schuler, John T Watson, Sankan Nyanseor, Melissa Briggs-Hagen, Sharon Saydah, Claire M Midgley, Kimberly Pringle, Helen Chu, Jesse D Bloom, Janet A Englund
doi:10.1101/2022.01.14.22269235

Abstract ​

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits an antibody response that targets several viral proteins including spike (S) and nucleocapsid (N); S is the major target of neutralizing antibodies. Here, we assess levels of anti-N binding antibodies and anti-S neutralizing antibodies in unvaccinated children compared with unvaccinated older adults following infection. Specifically, we examine neutralization and anti-N binding by sera collected up to 52 weeks following SARS-CoV-2 infection in children and compare these to a cohort of adults, including older adults, most of whom had mild infections that did not require hospitalization. Neutralizing antibody titers were lower in children than adults early after infection, but by 6 months titers were similar between age groups. The neutralizing activity of the children’s sera decreased modestly from one to six months; a pattern that was not significantly different from that observed in adults. However, infection of children induced much lower levels of anti-N antibodies than in adults, and levels of these anti-N antibodies decreased more rapidly in children than in adults, including older adults. These results highlight age-related differences in the antibody responses to SARS-CoV-2 proteins and, as vaccines for children are introduced, may provide comparator data for the longevity of infection-elicited and vaccination-induced neutralizing antibody responses.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2022_greaney_a.html b/papers/2022_greaney_a.html index 0448583..b82ea37 100644 --- a/papers/2022_greaney_a.html +++ b/papers/2022_greaney_a.html @@ -6,19 +6,19 @@ The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes | Bloom Lab - + - - - - + + + +
PLoS PathogensJune 29, 2022

The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes

Allison J Greaney, Rachel T Eguia, Tyler N Starr, Khadija Khan, Nicholas Franko, Jennifer K Logue, Sandra M Lord, Cate Speake, Helen Y Chu, Alex Sigal, Jesse D Bloom
doi:10.1371/journal.ppat.1010592

Abstract ​

Exposure histories to SARS-CoV-2 variants and vaccinations will shape the specificity of antibody responses. To understand the specificity of Delta-elicited antibody immunity, we characterize the polyclonal antibody response elicited by primary or mRNA vaccine-breakthrough Delta infections. Both types of infection elicit a neutralizing antibody response focused heavily on the receptor-binding domain (RBD). We use deep mutational scanning to show that mutations to the RBD’s class 1 and class 2 epitopes, including sites 417, 478, and 484–486 often reduce binding of these Delta-elicited antibodies. The anti-Delta antibody response is more similar to that elicited by early 2020 viruses than the Beta variant, with mutations to the class 1 and 2, but not class 3 epitopes, having the largest effects on polyclonal antibody binding. In addition, mutations to the class 1 epitope (e.g., K417N) tend to have larger effects on antibody binding and neutralization in the Delta spike than in the D614G spike, both for vaccine- and Delta-infection-elicited antibodies. These results help elucidate how the antigenic impacts of SARS-CoV-2 mutations depend on exposure history.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2022_greaney_b.html b/papers/2022_greaney_b.html index a75d7da..5ec6267 100644 --- a/papers/2022_greaney_b.html +++ b/papers/2022_greaney_b.html @@ -6,19 +6,19 @@ A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy | Bloom Lab - + - - - - + + + +
PLoS pathogensFebruary 8, 2022

A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy

Allison J Greaney, Tyler N Starr, Rachel T Eguia, Andrea N Loes, Khadija Khan, Farina Karim, Sandile Cele, John E Bowen, Jennifer K Logue, Davide Corti, David Veesler, Helen Y Chu, Alex Sigal, Jesse D Bloom
doi:10.1371/journal.ppat.1010248

Abstract ​

Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the “class 3” epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2022_greaney_c.html b/papers/2022_greaney_c.html index 04e21e7..44165ed 100644 --- a/papers/2022_greaney_c.html +++ b/papers/2022_greaney_c.html @@ -6,19 +6,19 @@ An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain | Bloom Lab - + - - - - + + + +
Virus EvolutionJanuary 1, 2022

An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain

Allison J Greaney, Tyler N Starr, Jesse D Bloom
doi:10.1093/ve/veac021

Abstract ​

A key goal of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surveillance is to rapidly identify viral variants with mutations that reduce neutralization by polyclonal antibodies elicited by vaccination or infection. Unfortunately, direct experimental characterization of new viral variants lags their sequence-based identification. Here we help address this challenge by aggregating deep mutational scanning data into an ‘escape estimator’ that estimates the antigenic effects of arbitrary combinations of mutations to the virus’s spike receptor-binding domain. The estimator can be used to intuitively visualize how mutations impact polyclonal antibody recognition and score the expected antigenic effect of combinations of mutations. These scores correlate with neutralization assays performed on SARS-CoV-2 variants and emphasize the ominous antigenic properties of the recently described Omicron variant. An interactive version of the estimator is at https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/ (last accessed 11 March 2022), and we provide a Python module for batch processing. Currently the calculator uses primarily data for antibodies elicited by Wuhan-Hu-1-like vaccination or infection and so is expected to work best for calculating escape from such immunity for mutations relative to early SARS-CoV-2 strains.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2022_hannon.html b/papers/2022_hannon.html index cc36059..79ee8e0 100644 --- a/papers/2022_hannon.html +++ b/papers/2022_hannon.html @@ -6,19 +6,19 @@ Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat | Bloom Lab - + - - - - + + + +
Virus EvolutionJuly 1, 2022

Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat

William W Hannon, Pavitra Roychoudhury, Hong Xie, Lasata Shrestha, Amin Addetia, Keith R Jerome, Alexander L Greninger, Jesse D Bloom
doi:10.1093/ve/veac052

Abstract ​

The long-term evolution of viruses is ultimately due to viral mutants that arise within infected individuals and transmit to other individuals. Here, we use deep sequencing to investigate the transmission of viral genetic variation among individuals during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak that infected the vast majority of crew members on a fishing boat. We deep-sequenced nasal swabs to characterize the within-host viral population of infected crew members, using experimental duplicates and strict computational filters to ensure accurate variant calling. We find that within-host viral diversity is low in infected crew members. The mutations that did fix in some crew members during the outbreak are not observed at detectable frequencies in any of the sampled crew members in which they are not fixed, suggesting that viral evolution involves occasional fixation of low-frequency mutations during transmission rather than persistent maintenance of within-host viral diversity. Overall, our results show that strong transmission bottlenecks dominate viral evolution even during a superspreading event with a very high attack rate.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2022_starr_a.html b/papers/2022_starr_a.html index cb481b1..82b77cf 100644 --- a/papers/2022_starr_a.html +++ b/papers/2022_starr_a.html @@ -6,19 +6,19 @@ ACE2 binding is an ancestral and evolvable trait of sarbecoviruses | Bloom Lab - + - - - - + + + +
NatureMarch 31, 2022

ACE2 binding is an ancestral and evolvable trait of sarbecoviruses

Tyler N Starr, Samantha K Zepeda, Alexandra C Walls, Allison J Greaney, Sergey Alkhovsky, David Veesler, Jesse D Bloom
doi:10.1038/s41586-022-04464-z

Abstract ​

Two different sarbecoviruses have caused major human outbreaks in the past two decades. Both of these sarbecoviruses, SARS-CoV-1 and SARS-CoV-2, engage ACE2 through the spike receptor-binding domain. However, binding to ACE2 orthologues of humans, bats and other species has been observed only sporadically among the broader diversity of bat sarbecoviruses. Here we use high-throughput assays to trace the evolutionary history of ACE2 binding across a diverse range of sarbecoviruses and ACE2 orthologues. We find that ACE2 binding is an ancestral trait of sarbecovirus receptor-binding domains that has subsequently been lost in some clades. Furthermore, we reveal that bat sarbecoviruses from outside Asia can bind to ACE2. Moreover, ACE2 binding is highly evolvable—for many sarbecovirus receptor-binding domains, there are single amino-acid mutations that enable binding to new ACE2 orthologues. However, the effects of individual mutations can differ considerably between viruses, as shown by the N501Y mutation, which enhances the human ACE2-binding affinity of several SARS-CoV-2 variants of concern but substantially decreases it for SARS-CoV-1. Our results point to the deep ancestral origin and evolutionary plasticity of ACE2 binding, broadening the range of sarbecoviruses that should be considered to have spillover potential.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2022_starr_greaney_a.html b/papers/2022_starr_greaney_a.html index c89f98a..8e479e8 100644 --- a/papers/2022_starr_greaney_a.html +++ b/papers/2022_starr_greaney_a.html @@ -6,19 +6,19 @@ Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains | Bloom Lab - + - - - - + + + +
PLoS pathogensNovember 18, 2022

Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains

Tyler N Starr*, Allison J Greaney*, Cameron M Stewart, Alexandra C Walls, William W Hannon, David Veesler, Jesse D Bloom
doi:10.1371/journal.ppat.1010951

Abstract ​

SARS-CoV-2 continues to acquire mutations in the spike receptor-binding domain (RBD) that impact ACE2 receptor binding, folding stability, and antibody recognition. Deep mutational scanning prospectively characterizes the impacts of mutations on these biochemical properties, enabling rapid assessment of new mutations seen during viral surveillance. However, the effects of mutations can change as the virus evolves, requiring updated deep mutational scans. We determined the impacts of all single amino acid mutations in the Omicron BA.1 and BA.2 RBDs on ACE2-binding affinity, RBD folding, and escape from binding by the LY-CoV1404 (bebtelovimab) monoclonal antibody. The effects of some mutations in Omicron RBDs differ from those measured in the ancestral Wuhan-Hu-1 background. These epistatic shifts largely resemble those previously seen in the Alpha variant due to the convergent epistatically modifying N501Y substitution. However, Omicron variants show additional lineage-specific shifts, including examples of the epistatic phenomenon of entrenchment that causes the Q498R and N501Y substitutions present in Omicron to be more favorable in that background than in earlier viral strains. In contrast, the Omicron substitution Q493R exhibits no sign of entrenchment, with the derived state, R493, being as unfavorable for ACE2 binding in Omicron RBDs as in Wuhan-Hu-1. Likely for this reason, the R493Q reversion has occurred in Omicron sub-variants including BA.4/BA.5 and BA.2.75, where the affinity buffer from R493Q reversion may potentiate concurrent antigenic change. Consistent with prior studies, we find that Omicron RBDs have reduced expression, and identify candidate stabilizing mutations that ameliorate this deficit. Last, our maps highlight a broadening of the sites of escape from LY-CoV1404 antibody binding in BA.1 and BA.2 compared to the ancestral Wuhan-Hu-1 background. These BA.1 and BA.2 deep mutational scanning datasets identify shifts in the RBD mutational landscape and inform ongoing efforts in viral surveillance.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2022_starr_greaney_b.html b/papers/2022_starr_greaney_b.html index ba3a9cd..378f584 100644 --- a/papers/2022_starr_greaney_b.html +++ b/papers/2022_starr_greaney_b.html @@ -6,19 +6,19 @@ Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution | Bloom Lab - + - - - - + + + +
ScienceJuly 22, 2022

Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution

Tyler N Starr*, Allison J Greaney*, William W Hannon, Andrea N Loes, Kevin Hauser, Josh R Dillen, Elena Ferri, Ariana Ghez Farrell, Bernadeta Dadonaite, Matthew McCallum, Kenneth A Matreyek, Davide Corti, David Veesler, Gyorgy Snell, Jesse D Bloom
doi:10.1126/science.abo7896

Abstract ​

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved variants with substitutions in the spike receptor-binding domain (RBD) that affect its affinity for angiotensin-converting enzyme 2 (ACE2) receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites—a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single–amino acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently Asn501→Tyr (N501Y), cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change—for example, enabling many of the antibody-escape substitutions in the Omicron RBD. These epistatic shifts occur despite high conservation of the overall RBD structure. Our data shed light on RBD sequence-function relationships and facilitate interpretation of ongoing SARS-CoV-2 evolution.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2022_yu.html b/papers/2022_yu.html index 6159051..5ab8ad9 100644 --- a/papers/2022_yu.html +++ b/papers/2022_yu.html @@ -6,19 +6,19 @@ A biophysical model of viral escape from polyclonal antibodies | Bloom Lab - + - - - - + + + +
Virus EvolutionJuly 1, 2022

A biophysical model of viral escape from polyclonal antibodies

Timothy C Yu, Zorian T Thornton, William W Hannon, William S DeWitt, Caelan E Radford, Frederick A Matsen IV, Jesse D Bloom
doi:10.1093/ve/veac110

Abstract ​

A challenge in studying viral immune escape is determining how mutations combine to escape polyclonal antibodies, which can potentially target multiple distinct viral epitopes. Here we introduce a biophysical model of this process that partitions the total polyclonal antibody activity by epitope and then quantifies how each viral mutation affects the antibody activity against each epitope. We develop software that can use deep mutational scanning data to infer these properties for polyclonal antibody mixtures. We validate this software using a computationally simulated deep mutational scanning experiment and demonstrate that it enables the prediction of escape by arbitrary combinations of mutations. The software described in this paper is available at https://jbloomlab.github.io/polyclonal.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2023_bacsik.html b/papers/2023_bacsik.html index 1e3abfe..25b1f6b 100644 --- a/papers/2023_bacsik.html +++ b/papers/2023_bacsik.html @@ -6,19 +6,19 @@ Influenza virus transcription and progeny production are poorly correlated in single cells | Bloom Lab - + - - - - + + + +
eLifeSeptember 7, 2023

Influenza virus transcription and progeny production are poorly correlated in single cells

David J Bacsik, Bernadeta Dadonaite, Andrew Butler, Allison J Greaney, Nicholas S Heaton, Jesse D Bloom
doi:10.7554/eLife.86852.2

Abstract ​

The ultimate success of a viral infection at the cellular level is determined by the number of progeny virions produced. However, most single-cell studies of infection quantify the expression of viral transcripts and proteins, rather than the amount of progeny virions released from infected cells. Here, we overcome this limitation by simultaneously measuring transcription and progeny production from single influenza virus-infected cells by embedding nucleotide barcodes in the viral genome. We find that viral transcription and progeny production are poorly correlated in single cells. The cells that transcribe the most viral mRNA do not produce the most viral progeny and often represent aberrant infections that fail to express the influenza NS gene. However, only some of the discrepancy between transcription and progeny production can be explained by viral gene absence or mutations: there is also a wide range of progeny production among cells infected by complete unmutated virions. Overall, our results show that viral transcription is a relatively poor predictor of an infected cell’s contribution to the progeny population.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2023_bloom_a.html b/papers/2023_bloom_a.html index 9c88a00..c43fca9 100644 --- a/papers/2023_bloom_a.html +++ b/papers/2023_bloom_a.html @@ -6,19 +6,19 @@ Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market | Bloom Lab - + - - - - + + + +
Virus EvolutionJuly 1, 2023

Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market

Jesse D Bloom
doi:10.1093/ve/vead050

Abstract ​

The role of the Huanan Seafood Market in the early severe acute respiratory syndrome virus 2 (SARS-CoV-2) outbreak remains unclear. Recently, the Chinese Centers for Disease Control (CDC) released data from deep sequencing of environmental samples collected from the market after it was closed on 1 January 2020. Prior to this release, Crits-Christoph et al. analyzed data from a subset of the samples. Both that study and the Chinese CDC study concurred that the samples contained genetic material from a variety of species, including some like raccoon dogs that are susceptible to SARS-CoV-2. However, neither study systematically analyzed the relationship between the amount of genetic material from SARS-CoV-2 and different animal species. Here I implement a fully reproducible computational pipeline that jointly analyzes the number of reads mapping to SARS-CoV-2 and the mitochondrial genomes of chordate species across the full set of samples. I validate the presence of genetic material from numerous species and calculate mammalian mitochondrial compositions similar to those reported by Crits-Christoph et al. However, the SARS-CoV-2 content of the environmental samples is generally very low: only 21 of 176 samples contain more than ten SARS-CoV-2 reads, despite most samples being sequenced to depths exceeding 10**8 total reads. None of the samples with double-digit numbers of SARS-CoV-2 reads have a substantial fraction of their mitochondrial material from any non-human susceptible species. Only one of the fourteen samples with at least a fifth of the chordate mitochondrial material from raccoon dogs contains any SARS-CoV-2 reads, and that sample only has 1 of ~200,000,000 reads mapping to SARS-CoV-2. Instead, SARS-CoV-2 reads are most correlated with reads mapping to various fish, such as catfish and largemouth bass. These results suggest that while metagenomic analysis of the environmental samples is useful for identifying animals or animal products sold at the market, co-mingling of animal and viral genetic material is unlikely to reliably indicate whether any animals were infected by SARS-CoV-2.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2023_bloom_b.html b/papers/2023_bloom_b.html index c803e94..4c13d39 100644 --- a/papers/2023_bloom_b.html +++ b/papers/2023_bloom_b.html @@ -6,19 +6,19 @@ Evolution of the SARS-CoV-2 mutational spectrum | Bloom Lab - + - - - - + + + +
Molecular Biology and EvolutionApril 11, 2023

Evolution of the SARS-CoV-2 mutational spectrum

Jesse D Bloom, Annabel C Beichman, Richard A Neher, Kelley Harris
doi:10.1093/molbev/msad085

Abstract ​

SARS-CoV-2 evolves rapidly in part because of its high mutation rate. Here, we examine whether this mutational process itself has changed during viral evolution. To do this, we quantify the relative rates of different types of single-nucleotide mutations at 4-fold degenerate sites in the viral genome across millions of human SARS-CoV-2 sequences. We find clear shifts in the relative rates of several types of mutations during SARS-CoV-2 evolution. The most striking trend is a roughly 2-fold decrease in the relative rate of G→T mutations in Omicron versus early clades, as was recently noted by Ruis et al. (2022. Mutational spectra distinguish SARS-CoV-2 replication niches. bioRxiv, doi:10.1101/2022.09.27.509649). There is also a decrease in the relative rate of C→T mutations in Delta, and other subtle changes in the mutation spectrum along the phylogeny. We speculate that these changes in the mutation spectrum could arise from viral mutations that affect genome replication, packaging, and antagonization of host innate-immune factors, although environmental factors could also play a role. Interestingly, the mutation spectrum of Omicron is more similar than that of earlier SARS-CoV-2 clades to the spectrum that shaped the long-term evolution of sarbecoviruses. Overall, our work shows that the mutation process is itself a dynamic variable during SARS-CoV-2 evolution and suggests that human SARS-CoV-2 may be trending toward a mutation spectrum more similar to that of other animal sarbecoviruses.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2023_bloom_c.html b/papers/2023_bloom_c.html index f730112..aef7d65 100644 --- a/papers/2023_bloom_c.html +++ b/papers/2023_bloom_c.html @@ -6,19 +6,19 @@ Fitness effects of mutations to SARS-CoV-2 proteins | Bloom Lab - + - - - - + + + +
Virus EvolutionSeptember 18, 2023

Fitness effects of mutations to SARS-CoV-2 proteins

Jesse D Bloom, Richard A Neher
doi:10.1093/ve/veae026

Abstract ​

Knowledge of the fitness effects of mutations to SARS-CoV-2 can inform assessment of new variants, design of therapeutics resistant to escape, and understanding of the functions of viral proteins. However, experimentally measuring effects of mutations is challenging: we lack tractable lab assays for many SARS-CoV-2 proteins, and comprehensive deep mutational scanning has been applied to only two SARS-CoV-2 proteins. Here, we develop an approach that leverages millions of publicly available SARS-CoV-2 sequences to estimate effects of mutations. We first calculate how many independent occurrences of each mutation are expected to be observed along the SARS-CoV-2 phylogeny in the absence of selection. We then compare these expected observations to the actual observations to estimate the effect of each mutation. These estimates correlate well with deep mutational scanning measurements. For most genes, synonymous mutations are nearly neutral, stop-codon mutations are deleterious, and amino acid mutations have a range of effects. However, some viral accessory proteins are under little to no selection. We provide interactive visualizations of effects of mutations to all SARS-CoV-2 proteins (https://jbloomlab.github.io/SARS2-mut-fitness/). The framework we describe is applicable to any virus for which the number of available sequences is sufficiently large that many independent occurrences of each neutral mutation are observed.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2023_dadonaite_crawford_radford.html b/papers/2023_dadonaite_crawford_radford.html index c8b73d6..d04b0b1 100644 --- a/papers/2023_dadonaite_crawford_radford.html +++ b/papers/2023_dadonaite_crawford_radford.html @@ -6,19 +6,19 @@ A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike | Bloom Lab - + - - - - + + + +
CellMarch 16, 2023

A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike

Bernadeta Dadonaite*, Katharine HD Crawford*, Caelan E Radford*, Ariana G Farrell, C Yu Timothy, William W Hannon, Panpan Zhou, Raiees Andrabi, Dennis R Burton, Lihong Liu, David D Ho, Helen Y Chu, Richard A Neher, Jesse D Bloom
doi:10.1016/j.cell.2023.02.001

Abstract ​

A major challenge in understanding SARS-CoV-2 evolution is interpreting the antigenic and functional effects of emerging mutations in the viral spike protein. Here, we describe a deep mutational scanning platform based on non-replicative pseudotyped lentiviruses that directly quantifies how large numbers of spike mutations impact antibody neutralization and pseudovirus infection. We apply this platform to produce libraries of the Omicron BA.1 and Delta spikes. These libraries each contain ∼7,000 distinct amino acid mutations in the context of up to ∼135,000 unique mutation combinations. We use these libraries to map escape mutations from neutralizing antibodies targeting the receptor-binding domain, N-terminal domain, and S2 subunit of spike. Overall, this work establishes a high-throughput and safe approach to measure how ∼105 combinations of mutations affect antibody neutralization and spike-mediated infection. Notably, the platform described here can be extended to the entry proteins of many other viruses.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2023_kikawa.html b/papers/2023_kikawa.html index f4dabfb..cea1253 100644 --- a/papers/2023_kikawa.html +++ b/papers/2023_kikawa.html @@ -6,19 +6,19 @@ The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies | Bloom Lab - + - - - - + + + +
Journal of VirologyNovember 30, 2023

The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies

Caroline Kikawa, Catiana H Cartwright-Acar, Jackson B Stuart, Maya Contreras, Lisa M Levoir, Matthew J Evans, Jesse D Bloom, Leslie Goo
doi:10.1128/jvi.01414-23

Abstract ​

Zika virus and dengue virus are co-circulating flaviviruses with a widespread endemic range. Eliciting broad and potent neutralizing antibodies is an attractive goal for developing a vaccine to simultaneously protect against these viruses. However, the capacity of viral mutations to confer escape from broadly neutralizing antibodies remains undescribed, due in part to limited throughput and scope of traditional approaches. Here, we use deep mutational scanning to map how all possible single amino acid mutations in Zika virus envelope protein affect neutralization by antibodies of varying breadth and potency. While all antibodies selected viral escape mutations, the mutations selected by broadly neutralizing antibodies conferred less escape relative to those selected by narrow, virus-specific antibodies. Surprisingly, even for broadly neutralizing antibodies with similar binding footprints, different single mutations led to escape, indicating distinct functional requirements for neutralization not captured by existing structures. Additionally, the antigenic effects of mutations selected by broadly neutralizing antibodies were conserved across divergent, albeit related, flaviviruses. Our approach identifies residues critical for antibody neutralization, thus comprehensively defining the as-yet-unknown functional epitopes of antibodies with clinical potential.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2023_radford.html b/papers/2023_radford.html index b5f7550..ede7c85 100644 --- a/papers/2023_radford.html +++ b/papers/2023_radford.html @@ -6,19 +6,19 @@ Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning | Bloom Lab - + - - - - + + + +
Cell Host & MicrobeJuly 12, 2023

Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning

Caelan E Radford, Philipp Schommers, Lutz Gieselmann, Katharine HD Crawford, Bernadeta Dadonaite, Timothy C Yu, Adam S Dingens, Julie Overbaugh, Florian Klein, Jesse D Bloom
doi:10.1016/j.chom.2023.05.025

Abstract ​

Understanding the specificities of human serum antibodies that broadly neutralize HIV can inform prevention and treatment strategies. Here, we describe a deep mutational scanning system that can measure the effects of combinations of mutations to HIV envelope (Env) on neutralization by antibodies and polyclonal serum. We first show that this system can accurately map how all functionally tolerated mutations to Env affect neutralization by monoclonal antibodies. We then comprehensively map Env mutations that affect neutralization by a set of human polyclonal sera that neutralize diverse strains of HIV and target the site engaging the host receptor CD4. The neutralizing activities of these sera target different epitopes, with most sera having specificities reminiscent of individual characterized monoclonal antibodies, but one serum targeting two epitopes within the CD4-binding site. Mapping the specificity of the neutralizing activity in polyclonal human serum will aid in assessing anti-HIV immune responses to inform prevention strategies.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2024_bloom.html b/papers/2024_bloom.html index f42bb4d..51343eb 100644 --- a/papers/2024_bloom.html +++ b/papers/2024_bloom.html @@ -6,19 +6,19 @@ Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market | Bloom Lab - + - - - - + + + +
Virus EvolutionJanuary 1, 2024

Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market

Jesse D Bloom
doi:10.1093/ve/vead089

Abstract ​

In March 2023, the Chinese CDC publicly released raw metagenomic sequencing data for environmental samples collected in early 2020 from the Huanan Seafood Market. Prior to that data release, some scientists had suggested that these samples could be informative for establishing if animals such as raccoon dogs had been infected with severe acute respiratory syndrome virus 2 (SARS-CoV-2). However, no one had analyzed how much SARS-CoV-2 was actually present in the metagenomic sequencing data. After the raw data became available, I fully analyzed the abundance of both viral and animal genetic material in the samples. That analysis, which was published in Virus Evolution, found that the SARS-CoV-2 content of most samples was very low and that the abundance of SARS-CoV-2 was most strongly associated with animals such as largemouth bass that are not plausible candidates for having been infected. Based on these results, I concluded that the metagenomic content of the samples was not informative for determining if any non-human animals in the market had been infected with SARS-CoV-2. One of the authors of an earlier study of these samples, Florence Débarre, recently submitted a response to my paper. Here, I reply in turn to explain why it is important to quantify the abundance of viral material before drawing conclusions from metagenomic sequencing. I also report new analyses of other animal coronaviruses in the samples and show that material from some other animal coronaviruses is much more abundant than SARS-CoV-2 in samples collected on the date when most wildlife stall sampling was performed. I further show that material from some of these animal coronaviruses is associated with the animals they probably infect but that no such association exists for SARS-CoV-2. Overall, these new analyses further emphasize the importance of quantifying the actual amount of viral material in metagenomic samples and underscore why the environmental samples from the Huanan Seafood Market are not informative for determining if any non-human animals were infected with SARS-CoV-2.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2024_carr.html b/papers/2024_carr.html index 8a87045..a193972 100644 --- a/papers/2024_carr.html +++ b/papers/2024_carr.html @@ -6,19 +6,19 @@ Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex | Bloom Lab - + - - - - + + + +
ImmunityJuly 15, 2024

Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex

Caleb R Carr*, Katharine HD Crawford*, Michael Murphy, Jared G Galloway, Hugh K Haddox, Frederick A Matsen, Kristian G Andersen, Neil P King, Jesse D Bloom
doi:10.1016/j.immuni.2024.06.013

Abstract ​

Lassa virus is estimated to cause thousands of human deaths per year, primarily due to spillovers from its natural host, Mastomys rodents. Efforts to create vaccines and antibody therapeutics must account for the evolutionary variability of Lassa virus’s glycoprotein complex (GPC), which mediates viral entry into cells and is the target of neutralizing antibodies. To map the evolutionary space accessible to GPC, we use pseudovirus deep mutational scanning to measure how nearly all GPC amino-acid mutations affect cell entry and antibody neutralization. Our experiments define functional constraints throughout GPC. We quantify how GPC mutations affect neutralization by a panel of monoclonal antibodies and show that all antibodies are escaped by mutations that exist among natural Lassa virus lineages. Overall, our work describes a biosafety-level-2 method to elucidate the mutational space accessible to GPC and shows how prospective characterization of antigenic variation could aid design of therapeutics and vaccines.

Interactive visualizations ​

The results described in this paper can be interactively visualized at https://dms-vep.org/LASV_Josiah_GP_DMS/

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2024_dadonaite_a.html b/papers/2024_dadonaite_a.html index ad882cf..19b10c5 100644 --- a/papers/2024_dadonaite_a.html +++ b/papers/2024_dadonaite_a.html @@ -6,19 +6,19 @@ Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades | Bloom Lab - + - - - - + + + +
NatureJuly 3, 2024

Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades

Bernadeta Dadonaite, Jack Brown, Teagan E McMahon, Ariana G Farrell, Marlin D Figgins, Daniel Asarnow, Cameron Stewart, Jimin Lee, Jenni Logue, Trevor Bedford, Ben Murrell, Helen Y Chu, David Veesler, Jesse D Bloom
doi:10.1038/s41586-024-07636-1

Abstract ​

SARS-CoV-2 variants acquire mutations in spike that promote immune evasion and impact other properties that contribute to viral fitness such as ACE2 receptor binding and cell entry. Knowledge of how mutations affect these spike phenotypes can provide insight into the current and potential future evolution of the virus. Here we use pseudovirus deep mutational scanning to measure how >9,000 mutations across the full XBB.1.5 and BA.2 spikes affect ACE2 binding, cell entry, or escape from human sera. We find that mutations outside the receptor-binding domain (RBD) have meaningfully impacted ACE2 binding during SARS-CoV-2 evolution. We also measure how mutations to the XBB.1.5 spike affect neutralization by serum from individuals who recently had SARS-CoV-2 infections. The strongest serum escape mutations are in the RBD at sites 357, 420, 440, 456, and 473—however, the antigenic impacts of these mutations vary across individuals. We also identify strong escape mutations outside the RBD; however many of them decrease ACE2 binding, suggesting they act by modulating RBD conformation. Notably, the growth rates of human SARS-CoV-2 clades can be explained in substantial part by the measured effects of mutations on spike phenotypes, suggesting our data could enable better prediction of viral evolution.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2024_dadonaite_b.html b/papers/2024_dadonaite_b.html index 2368036..2606646 100644 --- a/papers/2024_dadonaite_b.html +++ b/papers/2024_dadonaite_b.html @@ -6,19 +6,19 @@ Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance | Bloom Lab - + - - - - + + + +
bioRxivMay 23, 2024

Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance

Bernadeta Dadonaite, Jenny J Ahn, Jordan T Ort, Jin Yu, Colleen Furey, Annie Dosey, William W Hannon, Amy Vincent Baker, Richard J Webby, Neil P King, Yan Liu, Scott E Hensley, Thomas P Peacock, Louise H Moncla, Jesse D Bloom
doi:10.1101/2024.05.23.595634

Abstract ​

H5 influenza is considered a potential pandemic threat. Recently, H5 viruses belonging to clade 2.3.4.4b have caused large outbreaks in avian and multiple non-human mammalian species. Previous studies have identified molecular phenotypes of the viral hemagglutinin (HA) protein that contribute to pandemic potential in humans, including cell entry, receptor preference, HA stability, and reduced neutralization by polyclonal sera. However, prior experimental work has only measured how these phenotypes are affected by a handful of the >10,000 different possible amino-acid mutations to HA. Here we use pseudovirus deep mutational scanning to measure how all mutations to a 2.3.4.4b H5 HA affect each phenotype. We identify mutations that allow HA to better bind α2-6-linked sialic acids, and show that some viruses already carry mutations that stabilize HA. We also measure how all HA mutations affect neutralization by sera from mice and ferrets vaccinated against or infected with 2.3.4.4b H5 viruses. These antigenic maps enable rapid assessment of when new viral strains have acquired mutations that may create mismatches with candidate vaccine strains. Overall, the systematic nature of deep mutational scanning combined with the safety of pseudoviruses enables comprehensive measurements of the phenotypic effects of mutations that can inform real-time interpretation of viral variation observed during surveillance of H5 influenza.

Interactive visualizations ​

The results described in this paper can be interactively visualized at https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2024_hannon.html b/papers/2024_hannon.html index 4e2bf95..a615fa7 100644 --- a/papers/2024_hannon.html +++ b/papers/2024_hannon.html @@ -6,19 +6,19 @@ dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets | Bloom Lab - + - - - - + + + +
Journal of Open Source SoftwareJuly 17, 2024

dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets

William W Hannon, Jesse D Bloom
doi:10.21105/joss.06129

Abstract ​

Understanding how mutations impact a protein’s functions is valuable for many types of biological questions. High-throughput techniques such as deep-mutational scanning (DMS) have greatly expanded the number of mutation-function datasets. For instance, DMS has been used to determine how mutations to viral proteins affect antibody escape (Dadonaite et al. 2023), receptor affinity (Starr et al. 2020), and essential functions such as viral genome transcription and replication (Li et al. 2023). With the growth of sequence databases, in some cases the effects of mutations can also be inferred from phylogenies of natural sequences (Bloom and Neher 2023) (Figure 1).

The mutation-based data generated by these approaches is often best understood in the context of a protein’s 3D structure; for instance, to assess questions like how mutations that affect antibody escape relate to the physical antibody binding epitope on the protein. However, current approaches for visualizing mutation data in the context of a protein’s structure are often cumbersome and require multiple steps and softwares. To streamline the visualization of mutation-associated data in the context of a protein structure, we developed a web-based tool, dms-viz. With dms-viz, users can straightforwardly visualize mutation-based data such as those from DMS experiments in the context of a 3D protein model in an interactive format. See https://dms-viz.github.io/ to use dms-viz.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2024_larsen.html b/papers/2024_larsen.html index 88b198c..24687eb 100644 --- a/papers/2024_larsen.html +++ b/papers/2024_larsen.html @@ -6,19 +6,19 @@ Functional and antigenic landscape of the Nipah virus receptor binding protein | Bloom Lab - + - - - - + + + +
bioRxivApril 17, 2024

Functional and antigenic landscape of the Nipah virus receptor binding protein

Brendan B Larsen, Teagan McMahon, Jack T Brown, Zhaoqian Wang, Caelan E Radford, James E Crowe, David Veesler, Jesse D Bloom
doi:10.1101/2024.04.17.589977

Abstract ​

Nipah virus recurrently spills over to humans, causing fatal infections. The viral receptor-binding protein (RBP or G) attaches to host receptors and is a major target of neutralizing antibodies. Here we use deep mutational scanning to measure how all amino-acid mutations to the RBP affect cell entry, receptor binding, and escape from neutralizing antibodies. We identify functionally constrained regions of the RBP, including sites involved in oligomerization, along with mutations that differentially modulate RBP binding to its two ephrin receptors. We map escape mutations for six anti-RBP antibodies, and find that few antigenic mutations are present in natural Nipah strains. Our findings offer insights into the potential for functional and antigenic evolution of the RBP that can inform the development of antibody therapies and vaccines.

Interactive visualizations ​

The results described in this paper can be interactively visualized at https://dms-vep.org/Nipah_Malaysia_RBP_DMS/

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2024_loes.html b/papers/2024_loes.html index dce68b5..746e77c 100644 --- a/papers/2024_loes.html +++ b/papers/2024_loes.html @@ -6,19 +6,19 @@ High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains | Bloom Lab - + - - - - + + + +
bioRxivMarch 8, 2024

High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains

Andrea N Loes, Rosario Araceli L Tarabi, John Huddleston, Lisa Touyon, Sook San Wong, Samuel MS Cheng, Nancy HL Leung, William W Hannon, Trevor Bedford, Sarah Cobey, Benjamin J Cowling, Jesse D Bloom
doi:10.1101/2024.03.08.584176

Abstract ​

The high genetic diversity of influenza viruses means that traditional serological assays have too low throughput to measure serum antibody neutralization titers against all relevant strains. To overcome this challenge, we have developed a sequencing-based neutralization assay that simultaneously measures titers against many viral strains using small serum volumes via a workflow similar to traditional neutralization assays. The key innovation is to incorporate unique nucleotide barcodes into the hemagglutinin (HA) genomic segment, and then pool viruses with numerous different barcoded HA variants and quantify infectivity of all of them simultaneously using next-generation sequencing. With this approach, a single researcher performed the equivalent of 2,880 traditional neutralization assays (80 serum samples against 36 viral strains) in approximately one month. We applied the sequencing-based assay to quantify the impact of influenza vaccination on neutralization titers against recent human H1N1 strains for individuals who had or had not also received a vaccine in the previous year. We found that the viral strain specificities of the neutralizing antibodies elicited by vaccination vary among individuals, and that vaccination induced a smaller increase in titers for individuals who had also received a vaccine the previous year—although the titers six months after vaccination were similar in individuals with and without the previous-year vaccination. We also identified a subset of individuals with low titers to a subclade of recent H1N1 even after vaccination. This study demonstrates the utility of high-throughput sequencing-based neutralization assays that enable titers to be simultaneously measured against many different viral strains. We provide a detailed experimental protocol (DOI: https://dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1) and a computational pipeline (https://github.com/jbloomlab/seqneut-pipeline) for the sequencing-based neutralization assays to facilitate the use of this method by others.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/2024_welsh.html b/papers/2024_welsh.html index 2d5f158..629bf9d 100644 --- a/papers/2024_welsh.html +++ b/papers/2024_welsh.html @@ -6,19 +6,19 @@ Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin | Bloom Lab - + - - - - + + + +
Cell Host & MicrobeJuly 19, 2024

Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin

Frances C Welsh, Rachel T Eguia, Juhye M Lee, Hugh K Haddox, Jared Galloway, Nguyen Van Vinh Chau, Andrea N Loes, John Huddleston, Timothy C Yu, Mai Quynh Le, Nguyen TD Nhat, Nguyen Thi Le Thanh, Alexander L Greninger, Helen Y Chu, Janet A Englund, Trevor Bedford, Frederick A Matsen IV, Maciej F Boni, Jesse D Bloom
doi:10.1016/j.chom.2024.06.015

Abstract ​

Human influenza virus evolves to escape neutralization by polyclonal antibodies. However, we have a limited understanding of how the antigenic effects of viral mutations vary across the human population and how this heterogeneity affects virus evolution. Here, we use deep mutational scanning to map how mutations to the hemagglutinin (HA) proteins of two H3N2 strains, A/Hong Kong/45/2019 and A/Perth/16/2009, affect neutralization by serum from individuals of a variety of ages. The effects of HA mutations on serum neutralization differ across age groups in ways that can be partially rationalized in terms of exposure histories. Mutations that were fixed in influenza variants after 2020 cause greater escape from sera from younger individuals compared with adults. Overall, these results demonstrate that influenza faces distinct antigenic selection regimes from different age groups and suggest approaches to understand how this heterogeneous selection shapes viral evolution.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/papers/index.html b/papers/index.html index c98cf46..8c42c6b 100644 --- a/papers/index.html +++ b/papers/index.html @@ -6,19 +6,19 @@ Bloom Lab - + - - - - + + + +

Papers

Papers from the Bloom Lab team. See also Google Scholar for a complete list of publications.

Filter by Keywords

Key Papers

These papers exemplify key current areas of research in the lab.

All Papers

Below is a complete list of primary research papers from our group.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/people/andrea-loes.html b/people/andrea-loes.html index 4ba2104..369fee6 100644 --- a/people/andrea-loes.html +++ b/people/andrea-loes.html @@ -6,19 +6,19 @@ Staff Scientist/Lab Manager | Bloom Lab - + - - - - + + + +
Andrea Loes

Andrea Loes

Staff Scientist/Lab Manager

Andrea Loes, PhD is a staff scientist/lab manager for the Bloom Lab. She recently developed a high-throughput, sequencing-based method for running neutralization assays for influenza viruses and is currently applying this method to better understand the sources of diversity in the specificity of human serum antibodies to influenza viruses between different individuals.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/people/andrew-butler.html b/people/andrew-butler.html index c90f6b9..666b9ef 100644 --- a/people/andrew-butler.html +++ b/people/andrew-butler.html @@ -6,19 +6,19 @@ Postdoctoral Fellow | Bloom Lab - + - - - - + + + +
Andrew Butler

Andrew Butler

Postdoctoral Fellow

As a postdoc in the Bloom Lab, I am interested in developing and applying single-cell methods to better understand heterogeneity in the context of viral infections.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/people/arjun-aditham.html b/people/arjun-aditham.html index 4eeef75..2db52dd 100644 --- a/people/arjun-aditham.html +++ b/people/arjun-aditham.html @@ -6,19 +6,19 @@ Postdoctoral Fellow | Bloom Lab - + - - - - + + + +
Arjun Aditham

Arjun Aditham

Postdoctoral Fellow

As a postdoc in the Bloom Lab, I'm utilizing deep mutational scanning approaches to characterize the Rabies glycoprotein.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/people/bernadeta-dadonaite.html b/people/bernadeta-dadonaite.html index 2a6d994..9e39f13 100644 --- a/people/bernadeta-dadonaite.html +++ b/people/bernadeta-dadonaite.html @@ -6,19 +6,19 @@ Staff Scientist | Bloom Lab - + - - - - + + + +
Bernadeta Dadonaite

Bernadeta Dadonaite

Staff Scientist

Bernadeta is a staff scientist in the Bloom lab and works on deep mutational scanning of SARS-CoV-2 spike and H5 hemagglutinin.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/people/brendan-larsen.html b/people/brendan-larsen.html index 69a6b9a..cb5f342 100644 --- a/people/brendan-larsen.html +++ b/people/brendan-larsen.html @@ -6,19 +6,19 @@ Postdoctoral Fellow | Bloom Lab - + - - - - + + + +
Brendan Larsen

Brendan Larsen

Postdoctoral Fellow

Brendan Larsen is a Postdoctoral Fellow in the Bloom lab, where he studies the functional and antigenic evolution of Nipah virus. He is broadly interested in zoonotic viruses, in particular, bat and rodent-borne viruses that could potentially spillover into humans. He is funded by the Washington Research Foundation.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/people/caelan-radford.html b/people/caelan-radford.html index 3416b29..0851d15 100644 --- a/people/caelan-radford.html +++ b/people/caelan-radford.html @@ -6,19 +6,19 @@ Staff Scientist | Bloom Lab - + - - - - + + + +
Caelan Radford

Caelan Radford

Staff Scientist

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/people/caleb-carr.html b/people/caleb-carr.html index dfe6e9f..4d0fb25 100644 --- a/people/caleb-carr.html +++ b/people/caleb-carr.html @@ -6,19 +6,19 @@ Graduate Student | Bloom Lab - + - - - - + + + +
Caleb Carr

Caleb Carr

Graduate Student

As a graduate student in the Bloom lab, I am using our deep mutational scanning (DMS) pipeline to study the glycoprotein complex of Lassa virus.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/people/caroline-kikawa.html b/people/caroline-kikawa.html index 4c0a62f..86a1a94 100644 --- a/people/caroline-kikawa.html +++ b/people/caroline-kikawa.html @@ -6,19 +6,19 @@ Graduate Student | Bloom Lab - + - - - - + + + +
Caroline Kikawa

Caroline Kikawa

Graduate Student

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/people/cassandra-simonich.html b/people/cassandra-simonich.html index ca11edd..a93a9ed 100644 --- a/people/cassandra-simonich.html +++ b/people/cassandra-simonich.html @@ -6,19 +6,19 @@ Pediatric Infectious Disease Fellow | Bloom Lab - + - - - - + + + +
Cassandra Simonich

Cassandra Simonich

Pediatric Infectious Disease Fellow

Cassie Simonich, MD, PhD is a Pediatric Infectious Diseases Fellow at Seattle Children’s Hospital. In the Bloom Lab, she studies the antigenic evolution of Respiratory Syncytial Virus.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/people/index.html b/people/index.html index 75ec78c..49df48d 100644 --- a/people/index.html +++ b/people/index.html @@ -6,19 +6,19 @@ Bloom Lab - + - - - - + + + +

Meet the Team

Faculty

Jesse Bloom

Jesse Bloom

Principal Investigator

Grad Students

Caleb Carr

Caleb Carr

Graduate Student

Caroline Kikawa

Caroline Kikawa

Graduate Student

Jenny Ahn

Jenny Ahn

Graduate Student

Lizzie Plender

Lizzie Plender

Graduate Student

Lucas Kampman

Lucas Kampman

Graduate Student

Tim Yu

Tim Yu

Graduate Student

Postdocs

Andrew Butler

Andrew Butler

Postdoctoral Fellow

Arjun Aditham

Arjun Aditham

Postdoctoral Fellow

Brendan Larsen

Brendan Larsen

Postdoctoral Fellow

Cassandra Simonich

Cassandra Simonich

Pediatric Infectious Disease Fellow

Sara Sunshine

Sara Sunshine

Postdoctoral Fellow

Sheri Harari

Sheri Harari

Postdoctoral Fellow

Wenlin Ren

Wenlin Ren

Postdoctoral Fellow

Xiaohui Ju

Xiaohui Ju

Postdoctoral Fellow

Staff

Andrea Loes

Andrea Loes

Staff Scientist/Lab Manager

Bernadeta Dadonaite

Bernadeta Dadonaite

Staff Scientist

Caelan Radford

Caelan Radford

Staff Scientist

Teagan McMahon

Teagan McMahon

Research Technician

Will Hannon

Will Hannon

Data Scientist

Alumni

Postdocs

Tal Einav
2019 - 2023
Assistant Professor at the La Jolla Institute of Immunology in San Diego
Tyler Starr
2018 - 2023
Assistant Professor at the University of Utah
Karen Barnard
2020 - 2021
Senior Medical Writer at Pfizer
Alistair Russell
2014 - 2019
Assistant Professor at UCSD Division of Biological Sciences
Shirleen Soh
2015 - 2019
Head of Academic Research at National Research Foundation, Singapore
Jeremy Roop
2016 - 2019
Scientist at Berkeley Brewing Science
Orr Ashenberg
2013 - 2017
Associate Director, Computational Biology at Broad Institute of MIT and Harvard
Bargavi Thyagarajan
2011 - 2014
Scientific Project Manager at the Allen Institute for Brain Science

Graduate Students

Frances Welsh
2019 - 2024
Research Scientist at Amazon
David Bacsik
2017 - 2023
Finishing medical school
Lauren Gentles
2016 - 2022
Scientist III at Thermo Fisher Scientific
Allie Greaney
2016 - 2022
Internal medicine resident at UCSF
Kate Crawford
2017 - 2021
Laboratory Medicine and Pathology resident at UW
Sarah Hilton
2016 - 2020
Senior Scientist at Dyno Therapeutics
Adam Dingens
2015 - 2019
Director building a 'stealth mode' biotech company
Katherine Xue
2015 - 2019
Incoming Assistant Professor at the University of California, Irvine
Juhye Lee
2015 - 2019
Resident at Massachusetts General Hospital
Heather Machkovech
2014 - 2018
Internal Medicine resident at University of Wisconsin Hospital and Clinic
Hugh Haddox
2013 - 2017
Project Manager in Erick Matsen's lab at Fred Hutch
Mike Doud
2013 - 2017
Infectious Disease Fellow at UC San Diego Health
Kathryn Hooper
2012 - 2015
Senior Scientist at Sonoma Biotherapeutics

Staff Members

Ariana Farrell
2020 - 2023
Incoming PhD student at UW Molecular and Cellular Biology
Rosario Tarabi
2020 - 2024
Business student at Franciscan University of Steubenville
Rachel Eguia
2019 - 2021
Associate Scientist at Variant Bio
Keara Malone
2019 - 2021
Teaching English in Tochigi Prefecture, Japan
Ian Gong
2011 - 2014
Assistant Facility Manager at Stop & Shop

Undergraduate Researchers

Jonathan Mah
2018 - 2020
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Cameron Meikle
2018 - 2018
undefined
Noah Cassidy
2017 - 2018
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Jacob Kowalsky
2016 - 2018
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Alexandria Wilson
2017 - 2017
undefined
Jai Padmakumar
2014 - 2016
undefined
Lessane Ketema
2016 - 2016
undefined
Alex Heckert
2014 - 2015
undefined
Khrystyna Dilai
2014 - 2014
undefined
Kendra Ferrier
2014 - 2014
undefined
Brandon Pratt
2014 - 2014
undefined
Donna Leet
2012 - 2013
undefined
Ari Kaufman
2013 - 2013
undefined
Sam Schetterer
2011 - 2012
undefined

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/people/jenny-ahn.html b/people/jenny-ahn.html index 06581c0..e6128cf 100644 --- a/people/jenny-ahn.html +++ b/people/jenny-ahn.html @@ -6,19 +6,19 @@ Graduate Student | Bloom Lab - + - - - - + + + +
Jenny Ahn

Jenny Ahn

Graduate Student

As a Graduate student in the Bloom lab, I am using deep mutational scanning to study the evolution of pandemic potential avian influenza. I am interested in looking at how viruses evolve to improve our response to viral surveillance, vaccine development, and antibody engineering.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/people/jesse-bloom.html b/people/jesse-bloom.html index d685131..a316715 100644 --- a/people/jesse-bloom.html +++ b/people/jesse-bloom.html @@ -6,19 +6,19 @@ Principal Investigator | Bloom Lab - + - - - - + + + +
Jesse Bloom

Jesse Bloom

Principal Investigator

Jesse is a professor at the Fred Hutchinson Cancer Research Center and an Investigator the Howard Hughes Medical Institute. Jesse started his lab at the Fred Hutch in 2011. Prior to that, he received a BS in Biological Chemistry from the University of Chicago (where he worked with Susan Lindquist), a MPhil in Theoretical Chemistry from Cambridge University (where he worked with David Wales), a PhD in Chemistry from Caltech (where he worked with Frances Arnold), and postdoctoral training in Biology at Caltech (where he worked with David Baltimore).

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/people/lizzie-plender.html b/people/lizzie-plender.html index 1bae159..3d631a4 100644 --- a/people/lizzie-plender.html +++ b/people/lizzie-plender.html @@ -6,19 +6,19 @@ Graduate Student | Bloom Lab - + - - - - + + + +
Lizzie Plender

Lizzie Plender

Graduate Student

Lizzie is a graduate student in the Bloom lab studying genetic variation in mucins, a group of innate immunity proteins that play critical roles in pathogen entrapment in health and disease.
Lizzie is joint-advised by Evan Eichler.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/people/lucas-kampman.html b/people/lucas-kampman.html index 6b3ecda..be32aec 100644 --- a/people/lucas-kampman.html +++ b/people/lucas-kampman.html @@ -6,19 +6,19 @@ Graduate Student | Bloom Lab - + - - - - + + + +
Lucas Kampman

Lucas Kampman

Graduate Student

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/people/sara-sunshine.html b/people/sara-sunshine.html index be1c759..9f6fff1 100644 --- a/people/sara-sunshine.html +++ b/people/sara-sunshine.html @@ -6,19 +6,19 @@ Postdoctoral Fellow | Bloom Lab - + - - - - + + + +
Sara Sunshine

Sara Sunshine

Postdoctoral Fellow

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/people/sheri-harari.html b/people/sheri-harari.html index e949aa2..a31597a 100644 --- a/people/sheri-harari.html +++ b/people/sheri-harari.html @@ -6,19 +6,19 @@ Postdoctoral Fellow | Bloom Lab - + - - - - + + + +
Sheri Harari

Sheri Harari

Postdoctoral Fellow

Sheri is a postdoc in the Bloom Lab utilizing deep mutational scanning approaches to characterize the HCoV-229E spike glycoprotein.

Copyright © Jesse Bloom 2024-Present

- + \ No newline at end of file diff --git a/people/teagan-mcmahon.html b/people/teagan-mcmahon.html index d127b52..7ff9fa3 100644 --- a/people/teagan-mcmahon.html +++ b/people/teagan-mcmahon.html @@ -6,19 +6,19 @@ Research Technician | Bloom Lab - + - - - - + + + +
Teagan McMahon

Teagan McMahon

Research Technician

Copyright © Jesse Bloom 2024-Present

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Tim Yu

Tim Yu

Graduate Student

As a graduate student in the Bloom lab, I use deep mutational scanning to help predict seasonal H3N2 influenza evolution.

Copyright © Jesse Bloom 2024-Present

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Wenlin Ren

Wenlin Ren

Postdoctoral Fellow

Wenlin is a postdoctoral researcher in the Bloom lab utilizing deep mutation scanning to investigate the entry mechanisms and antigenic evolution of coronaviruses and flaviviruses.

Copyright © Jesse Bloom 2024-Present

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Will Hannon

Will Hannon

Data Scientist

As a Data Scientist in the Bloom Lab, I develop and implement computational approaches to study viral evolution and communicate with our data. I’m interested in improving access to the information-rich datasets we generate to aid in antigen engineering, therapeutic design, viral surveillance, and gaining a better understanding of viral evolution.

Copyright © Jesse Bloom 2024-Present

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Xiaohui Ju

Xiaohui Ju

Postdoctoral Fellow

As a postdoc in Bloom Lab, I utilize deep mutational scanning approaches to characterize the Chikungunya virus envelope protein and non-structural protein in both vertebrate and invertebrate cells.

Copyright © Jesse Bloom 2024-Present

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Deep mutational scanning of H5 influenza hemagglutinin

In a new study, we have measured how all mutations to the hemagglutinin (HA) of clade 2.3.4.4b H5 influenza affect molecular phenotypes relevant to pandemic risk. The data can be interactively visualized at https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/

Overview ​

H5 influenza from clade 2.3.4.4b has been causing outbreaks in numerous animals, including wild birds, poultry, cats, and cattle. There is concern that this virus could pose a potential risk to humans if it acquires additional mutations that improve its ability to infect or transmit in humans. From prior work, several molecular phenotypes of HA are known to contribute to pandemic risk.

In a new study led by Bernadeta Dadonaite, we used deep mutational scanning to measure how all HA amino-acid mutations affected key molecular phenotypes.

molecular phenotypes measured

To make these measurements safely, we used a previously described pseudovirus deep mutational scanning system that allows us to characterize the effects of mutations to viral entry proteins using single-cycle replicative lentiviral particles that can be safely studied at biosafety-level 2. Using this system, we made libraries that covered all amino-acid mutations to the current candidate vaccine strain HA for clade 2.3.4.4b H5 influenza.

pseudovirus schematic

First we measured how all mutations affected the ability of HA to mediate cell entry. These results can be visualized either using a heatmap or by projecting functional constraint onto the HA protein structure, as show below. Overall, these measurements identify functionally constrained regions of HA that are unlikely to mutate, and so form good targets for antibodies and other therapeutics.

cell entry heatmapcell entry structure

Next we measured how mutations affect HA's ability to mediate entry into 293T cells that express a2-6 versus a2-3 linked sialic acids, which is important because human transmissible viruses use a2-6. Below are mutations that increase a2-6 usage:

a2-6 usage

We also measured how mutations affect HA stability, which is important as increased HA stability is associated with increased airborne transmissibility. Below is a map of stability enhancing mutations, which tend to be located in helices in the fusion machinery and interfaces between the head and stalk domains:

stability

Finally, we measured how all the mutations affect neutralization by mouse and ferret sera. The key sites of neutralization escape are on the top of the HA head mostly in classically defined antigenic regions, although sites of escape differ a bit between mouse and ferret sera:

escape

To aid in using these data in surveillance, our collaborators (Jordan Ort and Louise Moncla) have integrated them into nextstrain (see here to color a phylogenetic tree by the measured phenotypes).

Angie Hinrichs has also integrated the data into the UShER H5 trees.

How to visualize and access the data ​

To make the data as accessible as possible for use by others, see

See also ​

See also Jesse's Twitter thread and some slides about the study.

Copyright © Jesse Bloom 2024-Present

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Bloom Lab Blog

A collection of thoughts, ideas, and projects from the Bloom Lab team.

Copyright © Jesse Bloom 2024-Present

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Python package to parse complex user-defined features from long-read PacBio sequencing.

Copyright © Jesse Bloom 2024-Present

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Snakemake pipeline for analyzing deep mutational scanning of barcoded viral entry proteins.

Copyright © Jesse Bloom 2024-Present

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Interactive web tool for visualizing mutation data on a protein structure.

Copyright © Jesse Bloom 2024-Present

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Check out the documentation

polyclonal

Python package for modeling mutational escape from polyclonal antibodies using deep mutational scanning data.

Check out the documentation

seqneut-pipeline

Snakemake pipeline for analyzing sequencing-based neutralization assays.

Check out the documentation

Copyright © Jesse Bloom 2024-Present

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Python package for fitting neutralization curves.

Copyright © Jesse Bloom 2024-Present

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Python package for modeling mutational escape from polyclonal antibodies using deep mutational scanning data.

Copyright © Jesse Bloom 2024-Present

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Snakemake pipeline for analyzing sequencing-based neutralization assays.

Copyright © Jesse Bloom 2024-Present

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Big Datasets and Viral Evolution

We also develop new ways to leverage large datasets to better understand viral evolution.

We have come up with a way to leverage the millions of publicly available SARS-CoV-2 sequences to estimate the effect of individual mutations on viral fitness (see this paper and these slides). We've also created a platform to visualize the mutational effects to aid in interpretation of viral evolution.

We have also integrated thousands of deep mutational scanning measurements into an antibody-escape calculator that was widely used during the SARS-CoV-2 pandemic to understand the antigenic effects of viral mutations.

We also have projects that involve analyzing the evolution of viruses within individual infected humans, and developing models to understand epistasis among viral mutations.

Copyright © Jesse Bloom 2024-Present

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Deep Mutational Scanning

Our lab uses deep mutational scanning to experimentally measure how tens-of-thousands of mutations to viral proteins affect key properties including function, immune escape, and receptor binding.

"Pseudovirus neutralization system"

We primarily perform these experiments using a pseudovirus system that allows us to safely characterize mutants of entry proteins from a wide range of viruses, including SARS-CoV-2 spike, influenza hemagglutinin, Lassa virus GPC, HIV envelope, and Nipah virus RBP.

Deep mutational scanning can inform efforts to forecast the evolution of human seasonal viruses and surveil the evolution of potential pandemic viruses. To facilitate the use of deep mutational scanning for these important goals, we develop interactive visualization tools and data analysis pipelines. See here for an example of how we analyze and visualize large datasets to inform the study of viral evolution.

Copyright © Jesse Bloom 2024-Present

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Interplay of Immunity and Viral Evolution

We study immunity and viral evolution at both the population and single-cell levels.

"Sequencing-based neutralization assay"

At the population level, differences in exposure history and immune imprinting lead human individuals to make antibody responses that target different regions of rapidly evolving viruses like influenza and SARS-CoV-2. This population heterogeneity has profound implications for viral evolution and disease susceptibility, as it causes viral mutations to impact the immunity of different individuals differently. We are characterizing this population heterogeneity using both deep mutational scanning and a sequencing based-neutralization assay we developed that increases the throughput of traditional neutralization assays by several orders of magnitude (see schematic at left).

At the single-cell level, we developed approaches to sequence viruses in single cells and quantify how many progeny each infected cell produces. We use these approaches to understand how viral variation impacts the outcome of infection in individual cells.

Copyright © Jesse Bloom 2024-Present

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