Skip to content
Merged
Show file tree
Hide file tree
Changes from all commits
Commits
File filter

Filter by extension

Filter by extension

Conversations
Failed to load comments.
Loading
Jump to
Jump to file
Failed to load files.
Loading
Diff view
Diff view
28 changes: 28 additions & 0 deletions papers/2025_larsen_f.md
Original file line number Diff line number Diff line change
@@ -0,0 +1,28 @@
---
layout: paper
title: "Functional and antigenic constraints on the Nipah virus fusion protein"
date: "2025-10-15"
authors:
- "Brendan B Larsen"
- "Sheri Harari"
- "Risako Gen"
- "Cameron Stewart"
- "David Veesler"
- "Jesse D Bloom"
journal: "bioRxiv"
doi: "10.1101/2025.10.15.682664"
link: "https://doi.org/10.1101/2025.10.15.682664"
image: "/assets/papers/2025_larsen_f.jpg"
keywords:
- "Nipah"
- "Deep mutational scanning"
- "Pseudovirus"
selected: true
---

## Abstract

Nipah virus is a highly pathogenic virus in the family _Paramyxoviridae_ that utilizes two distinct surface glycoproteins to infect cells. The receptor-binding protein (RBP) binds host receptors whereas the fusion protein (F) merges viral and host membranes. Here, we use non-replicative pseudoviruses to safely measure the effects of all F single amino-acid residue mutations on its cell entry function and neutralization by monoclonal antibodies. We compare mutational tolerance in F with previous experimental measurements for RBP and show that F is much more functionally constrained than the RBP. We also identify mutationally intolerant sites on the F trimer surface and core that are critical for proper function, and describe mutations that are candidates for stabilizing F in the prefusion conformation for vaccine design. We quantify how F mutations affect neutralization by six monoclonal antibodies, and show that the magnitude of mutational effects on neutralization varies among antibodies. Our measurements of mutational effects on Nipah virus F predict the ability of the antibodies to neutralize the related Hendra virus. Overall, our work defines the functional and antigenic constraints on the F protein from an important zoonotic virus.

## Interactive visualizations
The results described in this paper can be interactively visualized at [https://dms-vep.org/Nipah_Malaysia_F_DMS/](https://dms-vep.org/Nipah_Malaysia_F_DMS/)
Binary file added public/assets/papers/2025_larsen_f.jpg
Loading
Sorry, something went wrong. Reload?
Sorry, we cannot display this file.
Sorry, this file is invalid so it cannot be displayed.