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2 changes: 1 addition & 1 deletion papers/2023_bacsik.md
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Expand Up @@ -13,7 +13,7 @@ journal: "eLife"
doi: "10.7554/eLife.86852.2"
link: "https://elifesciences.org/articles/86852"
image: "/assets/papers/2023_bacsik.jpg"
selected: true
selected: false
keywords:
- "Single-cell sequencing"
- "Influenza"
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2 changes: 1 addition & 1 deletion papers/2023_dadonaite_crawford_radford.md
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Expand Up @@ -25,7 +25,7 @@ keywords:
- "SARS-CoV-2"
- "Deep mutational scanning"
- "Pseudovirus"
selected: true
selected: false
---

## Abstract
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32 changes: 32 additions & 0 deletions papers/2025_dadonaite_b.md
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---
layout: paper
title: "Spike mutations that affect the function and antigenicity of recent KP.3.1.1-like SARS-CoV-2 variants"
date: "2025-08-18"
authors:
- "Bernadeta Dadonaite"
- "Sheri Harari"
- "Brendan B Larsen"
- "Lucas Kampman"
- "Alex Harteloo"
- "Anna Elias-Warren"
- "Helen Y Chu"
- "Jesse D Bloom"
journal: "bioRxiv"
doi: "10.1101/2025.08.18.671001"
link: "https://doi.org/10.1101/2025.08.18.671001"
image: "/assets/papers/2025_dadonaite_b.png"
selected: false
keywords:
- "SARS-CoV-2"
- "Deep mutational scanning"
- "Immunity"
- "Imprinting"
- "Pseudovirus"
---

## Abstract

SARS-CoV-2 is under strong evolutionary selection to acquire mutations in its spike protein that reduce neutralization by human polyclonal antibodies. Here we use pseudovirus-based deep mutational scanning to measure how mutations to the spike from the recent KP.3.1.1 SARS-CoV-2 strain affect cell entry, binding to ACE2 receptor, RBD up/down motion, and neutralization by human sera and clinically relevant antibodies. The spike mutations that most affect serum antibody neutralization sometimes differ between sera collected before versus after recent vaccination or infection, indicating these exposures shift the neutralization immunodominance hierarchy. The sites where mutations cause the greatest reduction in neutralization by post-vaccination or infection sera include receptor-binding domain (RBD) sites 475, 478 and 487, all of which have mutated in recent SARS-CoV-2 variants. Multiple mutations outside the RBD affect sera neutralization as strongly as any RBD mutations by modulating RBD up/down movement. Some sites that affect RBD up/down movement have mutated in recent SARS-CoV-2 variants. Finally, we measure how spike mutations affect neutralization by three clinically relevant SARS-CoV-2 antibodies: VYD222, BD55-1205, and SA55. Overall, these results illuminate the current constraints and pressures shaping SARS-CoV-2 evolution, and can help with efforts to forecast possible future antigenic changes that may impact vaccines or clinical antibodies.

## Interactive visualizations
Interactive visualizations of the data from this study are at [https://dms-vep.org/SARS-CoV-2_KP.3.1.1_spike_DMS/](https://dms-vep.org/SARS-CoV-2_KP.3.1.1_spike_DMS/).
33 changes: 33 additions & 0 deletions papers/2025_xu.md
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---
layout: paper
title: "Determinants of human versus mosquito cell entry by the Chikungunya virus envelope proteins"
date: "2025-08-25"
authors:
- "Xiaohui Ju"
- "William W Hannon"
- "Tomasz Kaszuba"
- "Caelan E Radford"
- "Brendan B Larsen"
- "Samantha S Nelson"
- "Christopher A Nelson"
- "Israel Baltazar-Perez"
- "Ofer Zimmerman"
- "Daved H Fremont"
- "Michael S Diamond"
- "Jesse D Bloom"
journal: "bioRxiv"
doi: "10.1101/2025.08.25.672233"
link: "https://doi.org/10.1101/2025.08.25.672233"
image: "/assets/papers/2025_xu.png"
selected: true
keywords:
- "Chikungunya virus"
- "Deep mutational scanning"
- "Pseudovirus"
---

## Abstract
Chikungunya virus (CHIKV) infects both humans and mosquitoes during its transmission cycle. How the virus’s envelope proteins mediate entry in cells from such different species is unclear. MXRA8 is a receptor for CHIKV in mammalian cells, but the receptor(s) in mosquito cells remains unknown. Here we use pseudovirus deep mutational scanning to measure how nearly all amino-acid mutations to the CHIKV envelope proteins affect entry in MXRA8-expressing human and mosquito cells. Most mutations similarly affect entry in both types of cells, and our comprehensive measurements of these effects define functional constraints related to protein folding and fusion activity. However, some mutations differentially affect entry in MXRA8-expressing human cells versus mosquito cells. Sites where mutations specifically impair entry in MXRA8-expressing human cells are often involved in MXRA8 binding, and we hypothesize sites where mutations specifically impair entry in mosquito cells are involved in binding the unknown mosquito receptor(s). We use the deep mutational scanning data to design loss-of-tropism mutant viruses that are impaired in their ability to infect either mosquito cells or MXRA8-expressing human cells. Our findings provide insights into the species-specific determinants of CHIKV cell entry that can help guide receptor identification and vaccine development.

## Interactive visualizations
Interactive visualizations of the data from this study are at [https://dms-vep.org/CHIKV-181-25-E-DMS/](https://dms-vep.org/CHIKV-181-25-E-DMS/).
17 changes: 17 additions & 0 deletions posts/2025-08-18_kp311_dms.md
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---
layout: post
title: Spike mutations that affect the function and antigenicity of recent KP.3.1.1-like SARS-CoV-2 variants
date: 2025-08-18
author: Jesse Bloom
---

In a new study led by Bernadeta Dadaonaite and [posted on bioRxiv today](https://doi.org/10.1101/2025.08.18.671001), we used pseudovirus deep mutational scanning to understand how mutations affect the function and antigenicity of a recent SARS-CoV-2 variant that is fairly similar to those circulating right now.

---

For accessible summaries of the study, see:

- [This Bluesky thread](https://bsky.app/profile/jbloomlab.bsky.social/post/3lwsoohcdq22w), which can be read more easily in [threaded form here](https://skywriter.blue/pages/jbloomlab.bsky.social/post/3lwsoohcdq22w).
- [This X thread](https://x.com/jbloom_lab/status/1958035607575282092)

All the data are available for interactive visualization and download at [https://dms-vep.org/SARS-CoV-2_KP.3.1.1_spike_DMS/](https://dms-vep.org/SARS-CoV-2_KP.3.1.1_spike_DMS/).
18 changes: 18 additions & 0 deletions posts/2025-08-26_chikv_dms.md
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---
layout: post
title: Determinants of human versus mosquito cell entry by the Chikungunya virus envelope proteins
date: 2025-08-26
author: Jesse Bloom
---

In a new study led by Xiaohui Ju and [recently posted on bioRxiv](https://doi.org/10.1101/2025.08.25.672233), we measure how mutations the Chikungunya virus envelope proteins affect entry in human vs mosquito cells.
The results help elucidate how this virus can infect cells from such diverse species, and enable us to create loss-of-tropism mutants that can only efficiently infect cells from one species.

---

For accessible summaries of the study, see:

- [This Bluesky thread](https://bsky.app/profile/jbloomlab.bsky.social/post/3ly2bhapxd22j), which can be read more easily in [threaded form here](https://skywriter.blue/pages/jbloomlab.bsky.social/post/3ly2bhapxd22j).
- [This X thread](https://x.com/jbloom_lab/status/1963741826256658916).

All the data are available for interactive visualization and download at [https://dms-vep.org/CHIKV-181-25-E-DMS/](https://dms-vep.org/CHIKV-181-25-E-DMS/).
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