286: Deep mutational scanning of Nipah virus fusion protein F reveals functional and antigenic constraints

Larsen BB et al., Proc. Natl. Acad. Sci. U.S.A. 2026.123:e2529505123 - Deep mutational scanning of the Nipah virus fusion protein F using pseudoviruses maps ~8,500 single-residue effects, showing F is highly constrained and identifying antibody-escape mutations. Key terms: Nipah virus, fusion protein F, deep mutational scanning, pseudovirus, antibody neutralization.

Study Highlights:
Using nonreplicative lentiviral pseudoviruses and deep mutational scanning, the authors measured the effects of 8,449 single amino-acid mutations to the Nipah virus F ectodomain on cell entry in CHO cells expressing bat ephrin-B3. Measurements were fit with global epistasis models and mapped onto prefusion and postfusion structures, revealing the fusion peptide, lateral surface patches, and hexameric-interface residues are highly constrained. The library was screened against six monoclonal antibodies, quantifying mutation-mediated decreases in neutralization and showing distinct resilience among antibodies; specific Hendra F residues (Q70K, R336K) explained loss or reduction of neutralization by 4H3 and 1A9. The data nominate candidate proline substitutions and other sites for prefusion stabilization and inform vaccine and therapeutic antibody selection.

Conclusion:
Nipah virus F is highly functionally constrained relative to RBP with specific surface-exposed and core residues critical for cell entry, and antibody neutralization varies by epitope, informing prefusion-stabilized immunogen and therapeutic antibody design.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
Functional and antigenic constraints on the Nipah virus fusion protein

First author:
Larsen BB

Journal:
Proc. Natl. Acad. Sci. U.S.A. 2026.123:e2529505123

DOI:
10.1073/pnas.2529505123

Reference:
Larsen BB, Harari S, Gen R, Stewart C, Veesler D, Bloom JD. Functional and antigenic constraints on the Nipah virus fusion protein. Proc. Natl. Acad. Sci. U.S.A. 2026;123:e2529505123. https://doi.org/10.1073/pnas.2529505123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/

Support:
Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00

Official website https://basebybase.com

On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/nipah-f-deep-mutational-map

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-02-10.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the scientific content presented in the transcript, focusing on Nipah virus F deep mutational scanning, functional/antigenic constraints, structural interpretation, stabilizing mutations, antibody resilience, and translational implications.
- transcript topics: Nipah virus F structure and function; Deep mutational scanning methodology; Pseudovirus system with bat ephrin receptors; Mutational constraint landscape of Nipah F; Fusion peptide and hexamer interface regions; Prefusion stabilization via proline mutations

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 7
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- Nipah F is highly constrained; mutations mostly impair function
- Deep mutational scanning...