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Glyco-engineered MDCK cells display preferred receptors of H3N2 influenza absent in eggs used for vaccines

Author

Listed:
  • Chika Kikuchi

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Aristotelis Antonopoulos

    (Imperial College London)

  • Shengyang Wang

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Tadashi Maemura

    (University of Wisconsin-Madison)

  • Rositsa Karamanska

    (Imperial College London)

  • Chiara Lee

    (Imperial College London)

  • Andrew J. Thompson

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Anne Dell

    (Imperial College London)

  • Yoshihiro Kawaoka

    (University of Wisconsin-Madison
    Institute of Medical Science, The University of Tokyo
    National Center for Global Health and Medicine Research Institute
    The University of Tokyo)

  • Stuart M. Haslam

    (Imperial College London)

  • James C. Paulson

    (The Scripps Research Institute
    The Scripps Research Institute)

Abstract

Evolution of human H3N2 influenza viruses driven by immune selection has narrowed the receptor specificity of the hemagglutinin (HA) to a restricted subset of human-type (Neu5Acα2-6 Gal) glycan receptors that have extended poly-LacNAc (Galβ1-4GlcNAc) repeats. This altered specificity has presented challenges for hemagglutination assays, growth in laboratory hosts, and vaccine production in eggs. To assess the impact of extended glycan receptors on virus binding, infection, and growth, we have engineered N-glycan extended (NExt) cell lines by overexpressing β3-Ν-acetylglucosaminyltransferase 2 in MDCK, SIAT, and hCK cell lines. Of these, SIAT-NExt cells exhibit markedly increased binding of H3 HAs and susceptibility to infection by recent H3N2 virus strains, but without impacting final virus titers. Glycome analysis of these cell lines and allantoic and amniotic egg membranes provide insights into the importance of extended glycan receptors for growth of recent H3N2 viruses and relevance to their production for cell- and egg-based vaccines.

Suggested Citation

  • Chika Kikuchi & Aristotelis Antonopoulos & Shengyang Wang & Tadashi Maemura & Rositsa Karamanska & Chiara Lee & Andrew J. Thompson & Anne Dell & Yoshihiro Kawaoka & Stuart M. Haslam & James C. Paulson, 2023. "Glyco-engineered MDCK cells display preferred receptors of H3N2 influenza absent in eggs used for vaccines," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41908-0
    DOI: 10.1038/s41467-023-41908-0
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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.
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    Cited by:

    1. Luca Unione & Augustinus N. A. Ammerlaan & Gerlof P. Bosman & Elif Uslu & Ruonan Liang & Frederik Broszeit & Roosmarijn Woude & Yanyan Liu & Shengzhou Ma & Lin Liu & Marcos Gómez-Redondo & Iris A. Ber, 2024. "Probing altered receptor specificities of antigenically drifting human H3N2 viruses by chemoenzymatic synthesis, NMR, and modeling," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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