Show Notes
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 tested 8,449 single amino acid mutations (~98.2% coverage)
- F is more functionally constrained than RBP (RBP more mutationally tolerant)
- Fusion peptide and lateral surface/hexamer interfaces are highly constrained
- Proline substitutions can stabilize prefusion F (candidate stabilizing mutations identified)
- Monoclonal antibodies show varying resilience to F mutations; 1F2 and 2D3 retain neutralization more broadly
QC result: Pass.
