Epistasis mediates the evolution of the receptor binding mode in recent human H3N2 hemagglutinin

Ruipeng Lei, Weiwen Liang, Wenhao O. Ouyang, Andrea Hernandez Garcia, Chika Kikuchi, Shengyang Wang, Ryan McBride, Timothy J. C. Tan, Yuanxin Sun, Chunke Chen, Claire S. Graham, Lucia A. Rodriguez, Ivana R. Shen, Danbi Choi, Roberto Bruzzone, James C. Paulson, Satish K. Nair, Chris K. P. Mok () and Nicholas C. Wu ()
Additional contact information
Ruipeng Lei: University of Illinois Urbana-Champaign
Weiwen Liang: The University of Hong Kong
Wenhao O. Ouyang: University of Illinois Urbana-Champaign
Andrea Hernandez Garcia: University of Illinois Urbana-Champaign
Chika Kikuchi: The Scripps Research Institute
Shengyang Wang: The Scripps Research Institute
Ryan McBride: The Scripps Research Institute
Timothy J. C. Tan: University of Illinois Urbana-Champaign
Yuanxin Sun: The Chinese University of Hong Kong
Chunke Chen: The Chinese University of Hong Kong
Claire S. Graham: University of Illinois Urbana-Champaign
Lucia A. Rodriguez: University of Illinois Urbana-Champaign
Ivana R. Shen: University of Illinois Urbana-Champaign
Danbi Choi: University of Illinois Urbana-Champaign
Roberto Bruzzone: The University of Hong Kong
James C. Paulson: The Scripps Research Institute
Satish K. Nair: University of Illinois Urbana-Champaign
Chris K. P. Mok: The Chinese University of Hong Kong
Nicholas C. Wu: University of Illinois Urbana-Champaign

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract The receptor-binding site of influenza A virus hemagglutinin partially overlaps with major antigenic sites and constantly evolves. In this study, we observe that mutations G186D and D190N in the hemagglutinin receptor-binding site have coevolved in two recent human H3N2 clades. X-ray crystallography results show that these mutations coordinately drive the evolution of the hemagglutinin receptor binding mode. Epistasis between G186D and D190N is further demonstrated by glycan binding and thermostability analyses. Immunization and neutralization experiments using mouse and human samples indicate that the evolution of receptor binding mode is accompanied by a change in antigenicity. Besides, combinatorial mutagenesis reveals that G186D and D190N, along with other natural mutations in recent H3N2 strains, alter the compatibility with a common egg-adaptive mutation in seasonal influenza vaccines. Overall, our findings elucidate the role of epistasis in shaping the recent evolution of human H3N2 hemagglutinin and substantiate the high evolvability of its receptor-binding mode.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-49487-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49487-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-49487-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().