Genetic requirement for hemagglutinin glycosylation and its implications for influenza a H1N1 virus evolution

Jin Il Kim, Ilseob Lee, Sehee Park, Min Woong Hwang, Joon Yong Bae, Sangmoo Lee, Jun Heo, Mee Sook Park, Adolfo García-Sastre, Man Seong Park

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36 Citations (Scopus)

Abstract

Influenza A virus has evolved and thrived in human populations. Since the 1918 influenza A pandemic, human H1N1 viruses had acquired additional N-linked glycosylation (NLG) sites within the globular head region of hemagglutinin (HA) until the NLGfree HA head pattern of the 1918 H1N1 virus was renewed with the swine-derived 2009 pandemic H1N1 virus. Moreover, the HA of the 2009 H1N1 virus appeared to be antigenically related to that of the 1918 H1N1 virus. Hence, it is possible that descendants of the 2009 H1N1 virus might recapitulate the acquisition of HA head glycosylation sites through their evolutionary drift as a means to evade preexisting immunity. We evaluate here the evolution signature of glycosylations found in the globular head region of H1 HA in order to determine their impact in the virulence and transmission of H1N1 viruses. We identified a polymorphism at HA residue 147 associated with the acquisition of glycosylation at residues 144 and 172. By in vitro and in vivo analyses using mutant viruses, we also found that the polymorphism at HA residue 147 compensated for the loss of replication, virulence, and transmissibility associated with the presence of the N-linked glycans. Our findings suggest that the polymorphism in H1 HA at position 147 modulates viral fitness by buffering the constraints caused by N-linked glycans and provide insights into the evolution dynamics of influenza viruses with implications in vaccine immunogenicity.

Original languageEnglish
Pages (from-to)7539-7549
Number of pages11
JournalJournal of virology
Volume87
Issue number13
DOIs
Publication statusPublished - 2013 Jul 1

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Kim, J. I., Lee, I., Park, S., Hwang, M. W., Bae, J. Y., Lee, S., Heo, J., Park, M. S., García-Sastre, A., & Park, M. S. (2013). Genetic requirement for hemagglutinin glycosylation and its implications for influenza a H1N1 virus evolution. Journal of virology, 87(13), 7539-7549. https://doi.org/10.1128/JVI.00373-13