Revealing the Specificity of Human H1 Influenza A Viruses to Complex N-Glycans

Angeles Canales*, Javier Sastre, Jose M. Orduña, Cindy M. Spruit, Javier Pérez-Castells, Gema Domínguez, Kim M. Bouwman, Roosmarijn van der Woude, Francisco Javier Cañada, Corwin M. Nycholat, James C. Paulson, Geert Jan Boons, Jesús Jiménez-Barbero, Robert P. de Vries*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Influenza virus infection remains a threat to human health since viral hemagglutinins are constantly drifting, escaping infection and vaccine-induced antibody responses. Viral hemagglutinins from different viruses display variability in glycan recognition. In this context, recent H3N2 viruses have specificity for α2,6 sialylated branched N-glycans with at least three N-acetyllactosamine units (tri-LacNAc). In this work, we combined glycan arrays and tissue binding analyses with nuclear magnetic resonance experiments to characterize the glycan specificity of a family of H1 variants, including the one responsible for the 2009 pandemic outbreak. We also analyzed one engineered H6N1 mutant to understand if the preference for tri-LacNAc motifs could be a general trend in human-type receptor-adapted viruses. In addition, we developed a new NMR approach to perform competition experiments between glycans with similar compositions and different lengths. Our results point out that pandemic H1 viruses differ from previous seasonal H1 viruses by a strict preference for a minimum of di-LacNAc structural motifs.

Original languageEnglish
Pages (from-to)868-878
Number of pages11
JournalJACS Au
Volume3
Issue number3
DOIs
Publication statusPublished - 27 Mar 2023

Bibliographical note

Funding Information:
R.P.d.V. is a recipient of an ERC Starting grant from the European Commission (802780) and a Beijerinck Premium of the Royal Dutch Academy of Sciences. The glycan array setup was supported by the Netherlands Organization for Scientific Research (NWO, TOP-PUNT 718.015.003 to G.-J.P.H.B.). Dr. Lin Liu (CCRC) and Dr. Margreet A. Wolfert (Utrecht University) developed, printed, and validated the glycan microarray. We would like to thank Nikoloz Nemanichvili for technical assistance. A.C. acknowledges funding from Agencia Estatal de Investigación “Spanish Ministry of Science and Innovation” (MICINN) project PID2019-105237GB-I00. J.P.C. acknowledges funding by the Spanish MICINN, grant no. RTI2018-095588-B-I00 (co-funded by the European Regional Development Fund/European Social Fund, “Investing in your future”). JJB also thanks funding by the European Research Council (RECGLYCANMR, Advanced grant no. 788143), the Agencia Estatal de Investigación (Spain) for grants RTI2018-094751-B-C21 and C22 and PDI2021-1237810B–C21 and C22, and CIBERES, an initiative of the Instituto de Salud Carlos III (ISCIII), Madrid, Spain. The NMR spectra were acquired at the NMR service of CIB Margarita Salas and in the NMR facility of the UCM. We also acknowledge Prof. Robert Woods group for sending us the coordinates of a glycan-hemagglutinin model.

Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society.

Funding

R.P.d.V. is a recipient of an ERC Starting grant from the European Commission (802780) and a Beijerinck Premium of the Royal Dutch Academy of Sciences. The glycan array setup was supported by the Netherlands Organization for Scientific Research (NWO, TOP-PUNT 718.015.003 to G.-J.P.H.B.). Dr. Lin Liu (CCRC) and Dr. Margreet A. Wolfert (Utrecht University) developed, printed, and validated the glycan microarray. We would like to thank Nikoloz Nemanichvili for technical assistance. A.C. acknowledges funding from Agencia Estatal de Investigación “Spanish Ministry of Science and Innovation” (MICINN) project PID2019-105237GB-I00. J.P.C. acknowledges funding by the Spanish MICINN, grant no. RTI2018-095588-B-I00 (co-funded by the European Regional Development Fund/European Social Fund, “Investing in your future”). JJB also thanks funding by the European Research Council (RECGLYCANMR, Advanced grant no. 788143), the Agencia Estatal de Investigación (Spain) for grants RTI2018-094751-B-C21 and C22 and PDI2021-1237810B–C21 and C22, and CIBERES, an initiative of the Instituto de Salud Carlos III (ISCIII), Madrid, Spain. The NMR spectra were acquired at the NMR service of CIB Margarita Salas and in the NMR facility of the UCM. We also acknowledge Prof. Robert Woods group for sending us the coordinates of a glycan-hemagglutinin model.

Keywords

  • glycan array
  • influenza virus
  • N-glycan
  • NMR
  • recognition

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