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

Author

Listed:
  • 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
    The Scripps Research Institute)

  • Shengyang Wang

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Ryan McBride

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Timothy J. C. Tan

    (University of Illinois Urbana-Champaign)

  • Yuanxin Sun

    (The Chinese University of Hong Kong
    The Chinese University of Hong Kong)

  • Chunke Chen

    (The Chinese University of Hong Kong
    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
    Institut Pasteur
    Hong Kong Science Park)

  • James C. Paulson

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Satish K. Nair

    (University of Illinois Urbana-Champaign
    University of Illinois Urbana-Champaign
    University of Illinois Urbana-Champaign)

  • Chris K. P. Mok

    (The Chinese University of Hong Kong
    The Chinese University of Hong Kong
    The Chinese University of Hong Kong
    The Chinese University of Hong Kong)

  • Nicholas C. Wu

    (University of Illinois Urbana-Champaign
    University of Illinois Urbana-Champaign
    University of Illinois Urbana-Champaign
    University of Illinois Urbana-Champaign)

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.

Suggested Citation

  • 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. Ro, 2024. "Epistasis mediates the evolution of the receptor binding mode in recent human H3N2 hemagglutinin," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49487-4
    DOI: 10.1038/s41467-024-49487-4
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    References listed on IDEAS

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    1. Frederik Broszeit & Rosanne J. Beek & Luca Unione & Theo M. Bestebroer & Digantkumar Chapla & Jeong-Yeh Yang & Kelley W. Moremen & Sander Herfst & Ron A. M. Fouchier & Robert P. Vries & Geert-Jan Boon, 2021. "Glycan remodeled erythrocytes facilitate antigenic characterization of recent A/H3N2 influenza viruses," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. Peter S. Lee & Nobuko Ohshima & Robyn L. Stanfield & Wenli Yu & Yoshitaka Iba & Yoshinobu Okuno & Yoshikazu Kurosawa & Ian A. Wilson, 2014. "Receptor mimicry by antibody F045–092 facilitates universal binding to the H3 subtype of influenza virus," Nature Communications, Nature, vol. 5(1), pages 1-9, May.
    3. Nicholas C. Wu & Andrew J. Thompson & Jia Xie & Chih-Wei Lin & Corwin M. Nycholat & Xueyong Zhu & Richard A. Lerner & James C. Paulson & Ian A. Wilson, 2018. "A complex epistatic network limits the mutational reversibility in the influenza hemagglutinin receptor-binding site," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
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