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Probing altered receptor specificities of antigenically drifting human H3N2 viruses by chemoenzymatic synthesis, NMR, and modeling

Author

Listed:
  • Luca Unione

    (Utrecht University
    Basque Research & Technology Alliance (BRTA)
    Basque Foundation for Science)

  • Augustinus N. A. Ammerlaan

    (Utrecht University)

  • Gerlof P. Bosman

    (Utrecht University)

  • Elif Uslu

    (Utrecht University)

  • Ruonan Liang

    (Utrecht University)

  • Frederik Broszeit

    (Utrecht University)

  • Roosmarijn Woude

    (Utrecht University)

  • Yanyan Liu

    (Utrecht University)

  • Shengzhou Ma

    (University of Georgia)

  • Lin Liu

    (University of Georgia)

  • Marcos Gómez-Redondo

    (Basque Research & Technology Alliance (BRTA))

  • Iris A. Bermejo

    (Basque Research & Technology Alliance (BRTA))

  • Pablo Valverde

    (Basque Research & Technology Alliance (BRTA))

  • Tammo Diercks

    (Basque Research & Technology Alliance (BRTA))

  • Ana Ardá

    (Basque Research & Technology Alliance (BRTA)
    Basque Foundation for Science)

  • Robert P. Vries

    (Utrecht University)

  • Geert-Jan Boons

    (Utrecht University
    University of Georgia
    Utrecht University
    University of Georgia)

Abstract

Prototypic receptors for human influenza viruses are N-glycans carrying α2,6-linked sialosides. Due to immune pressure, A/H3N2 influenza viruses have emerged with altered receptor specificities that bind α2,6-linked sialosides presented on extended N-acetyl-lactosamine (LacNAc) chains. Here, binding modes of such drifted hemagglutinin’s (HAs) are examined by chemoenzymatic synthesis of N-glycans having 13C-labeled monosaccharides at strategic positions. The labeled glycans are employed in 2D STD-1H by 13C-HSQC NMR experiments to pinpoint which monosaccharides of the extended LacNAc chain engage with evolutionarily distinct HAs. The NMR data in combination with computation and mutagenesis demonstrate that mutations distal to the receptor binding domain of recent HAs create an extended binding site that accommodates with the extended LacNAc chain. A fluorine containing sialoside is used as NMR probe to derive relative binding affinities and confirms the contribution of the extended LacNAc chain for binding.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47344-y
    DOI: 10.1038/s41467-024-47344-y
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    References listed on IDEAS

    as
    1. 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.
    2. 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.
    3. Sigrid Gouma & Madison Weirick & Scott E. Hensley, 2020. "Antigenic assessment of the H3N2 component of the 2019-2020 Northern Hemisphere influenza vaccine," Nature Communications, Nature, vol. 11(1), pages 1-5, December.
    4. 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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