Influenza A virus hemagglutinin glycosylation compensates for antibody escape fitness costs

Ivan Kosik, William L. Ince, Lauren E. Gentles, Andrew J. Oler, Martina Kosikova, Matthew Angel, Javier G. Magadán, Hang Xie, Christopher B. Brooke, Jonathan W. Yewdell

Research output: Contribution to journalArticle

Abstract

Rapid antigenic evolution enables the persistence of seasonal influenza A and B viruses in human populations despite widespread herd immunity. Understanding viral mechanisms that enable antigenic evolution is critical for designing durable vaccines and therapeutics. Here, we utilize the primerID method of error-correcting viral population sequencing to reveal an unexpected role for hemagglutinin (HA) glycosylation in compensating for fitness defects resulting from escape from anti-HA neutralizing antibodies. Antibody-free propagation following antigenic escape rapidly selected viruses with mutations that modulated receptor binding avidity through the addition of N-linked glycans to the HA globular domain. These findings expand our understanding of the viral mechanisms that maintain fitness during antigenic evolution to include glycan addition, and highlight the immense power of high-definition virus population sequencing to reveal novel viral adaptive mechanisms.

Original languageEnglish (US)
Article numbere1006796
JournalPLoS pathogens
Volume14
Issue number1
DOIs
StatePublished - Jan 2018

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Influenza A virus
Hemagglutinins
Glycosylation
Costs and Cost Analysis
Polysaccharides
Antibodies
Herd Immunity
Population
Viruses
Influenza B virus
Neutralizing Antibodies
Vaccines
Mutation
Therapeutics

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Kosik, I., Ince, W. L., Gentles, L. E., Oler, A. J., Kosikova, M., Angel, M., ... Yewdell, J. W. (2018). Influenza A virus hemagglutinin glycosylation compensates for antibody escape fitness costs. PLoS pathogens, 14(1), [e1006796]. https://doi.org/10.1371/journal.ppat.1006796

Influenza A virus hemagglutinin glycosylation compensates for antibody escape fitness costs. / Kosik, Ivan; Ince, William L.; Gentles, Lauren E.; Oler, Andrew J.; Kosikova, Martina; Angel, Matthew; Magadán, Javier G.; Xie, Hang; Brooke, Christopher B.; Yewdell, Jonathan W.

In: PLoS pathogens, Vol. 14, No. 1, e1006796, 01.2018.

Research output: Contribution to journalArticle

Kosik, I, Ince, WL, Gentles, LE, Oler, AJ, Kosikova, M, Angel, M, Magadán, JG, Xie, H, Brooke, CB & Yewdell, JW 2018, 'Influenza A virus hemagglutinin glycosylation compensates for antibody escape fitness costs', PLoS pathogens, vol. 14, no. 1, e1006796. https://doi.org/10.1371/journal.ppat.1006796
Kosik, Ivan ; Ince, William L. ; Gentles, Lauren E. ; Oler, Andrew J. ; Kosikova, Martina ; Angel, Matthew ; Magadán, Javier G. ; Xie, Hang ; Brooke, Christopher B. ; Yewdell, Jonathan W. / Influenza A virus hemagglutinin glycosylation compensates for antibody escape fitness costs. In: PLoS pathogens. 2018 ; Vol. 14, No. 1.
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