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. 2025 May 1;188(9):2480-2494.e22.
doi: 10.1016/j.cell.2025.02.030. Epub 2025 Mar 24.

Functional and antigenic landscape of the Nipah virus receptor-binding protein

Brendan B Larsen  1 , Teagan McMahon  1 , Jack T Brown  2 , Zhaoqian Wang  2 , Caelan E Radford  1 , James E Crowe Jr  3 , David Veesler  4 , Jesse D Bloom  5
Affiliations

Functional and antigenic landscape of the Nipah virus receptor-binding protein

Brendan B Larsen et al. Cell. .

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.

Keywords: Nipah; deep mutational scanning; virus evolution.

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Conflict of interest statement

Declaration of interests J.D.B. is on the scientific advisory boards of Apriori Bio, Invivyd, and the Vaccine Company. J.D.B. consults for GlaxoSmithKline and Pfizer. J.D.B. receives royalty payments as an inventor on Fred Hutch-licensed patents related to viral DMS. J.E.C. has served as a consultant for Luna Labs USA, Merck Sharp & Dohme Corporation, Emergent Biosolutions, GlaxoSmithKline, and BTG International Inc. J.E.C. is a member of the scientific advisory board of Meissa Vaccines, a former member of the Scientific Advisory Board of Gigagen (Grifols), and is founder of IDBiologics. The laboratory of J.E.C. received unrelated sponsored research agreements from AstraZeneca, Takeda, and IDBiologics during the conduct of the study. Vanderbilt University has applied for a patent pertinent to some of the materials in this paper.

Update of

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