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Changes in the Receptor-Binding Properties of H3N2 Viruses during Long-Term Circulation in Humans

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Abstract

It was previously shown that hemagglutinin residues Thrl55, Glul58, and Ser228 are crucial for the recognition of Neu5Gc. In this study, we demonstrated that the ability to bind the Neu5Gc-terminated receptor is related to the amino acid 145: viruses of years 1972–1999 with Lysl45bindto the receptor, whereas viruses with Asnl 45 do not. Sporadic appearance and disappearance of the ability to bind Neu5Gc oligosaccharides and the absence of Neu5Gc in the composition of human glycoconjugates indicate the non-adaptive nature of this ability. It was previously shown that unlike H1N1 viruses, H3N2 viruses of years 1968–1989 did not distinguish between Neu5Acα2-6Galβ1-4Glc (6′SL) and Neu5Acα2-6Galβ1-4GlcNAc (6′SLN). H3N2 viruses isolated after 1993 have acquired the ability to distinguish between 6’SL and 6′SLN, similarly to H1N1 viruses. We found that the affinity for 6′SLN has gradually increased from 1992 to 2003. After 2003, the viruses lost the ability to bind a number of sialosides, including 6′SL, that were good receptors for earlier H3N2 viruses, and retained high affinity for 6′SLN only, which correlated with the acquisition of new glycosylation sites at positions 122, 133, and 144, as well as Glul90Asp and Gly225Asp substitutions, in hemagglutinin. These substitutions are also responsible for the receptor-binding phenotype of human H1N1 viruses. We conclude that the convergent evolution of the receptor specificity of the H1N1 and H3N2 viruses indicates that 6’SLN is the optimal natural human receptor for influenza viruses.

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Abbreviations

CE:

embryonated chicken egg

Glyc-PAA:

glycosylated polyacrylamide

Glyc-PAA-biotin:

biotinylated glycosylated polyacrylamide

HA:

hemagglutinin

NA:

neuraminidase

RBS:

receptor-binding site

Sia:

sialic acid (either Neu5Ac or Neu5Gc)

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Acknowledgements

We regret to inform that our colleague Alexander Klimov has died.

Funding

This study was supported by the Russian Foundation for Basic Research (projects 02-04-48109, 01-04-49300, 14-04-00547, and 17-04-00148) and the International Science and Technology Center (grant no. 5-2464).

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Authors and Affiliations

  1. Chumakov Federal Scientific Center for Research and Development of Immune and Biological Products, Russian Academy of Sciences, 108819, Moscow, Russia

    A. S. Gambaryan

  2. Influenza Branch, Centers for Disease Control and Prevention, GA, 30333, Atlanta, USA

    A. Balish & A. I. Klimov

  3. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia

    A. B. Tuzikov, A. A. Chinarev, G. V. Pazynina & N. V. Bovin

Authors
  1. A. S. Gambaryan
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  2. A. Balish
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  3. A. I. Klimov
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  4. A. B. Tuzikov
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  5. A. A. Chinarev
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  6. G. V. Pazynina
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  7. N. V. Bovin
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Corresponding author

Correspondence to A. S. Gambaryan.

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Conflict of interest. The authors declare no conflict of interest in financial or any other sphere.

Ethical approval. This article does not contain any studies with animals or human participants performed by any of the authors.

Additional information

Published in Russian in Biokhimiya, 2019, Vol. 84, No. 10, pp. 1450–1459.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM19-109, August 26, 2019.

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Gambaryan, A.S., Balish, A., Klimov, A.I. et al. Changes in the Receptor-Binding Properties of H3N2 Viruses during Long-Term Circulation in Humans. Biochemistry Moscow 84, 1177–1185 (2019). https://doi.org/10.1134/S0006297919100067

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