Influenza A virus hemagglutinin glycosylation compensates for antibody escape fitness costs

PLoS Pathog. 2018 Jan 18;14(1):e1006796. doi: 10.1371/journal.ppat.1006796. eCollection 2018 Jan.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Viral / immunology*
  • Antibodies, Viral / metabolism
  • Antigenic Variation* / genetics
  • Dogs
  • Genetic Fitness
  • Glycosylation
  • HEK293 Cells
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism*
  • Humans
  • Immune Evasion* / genetics
  • Immune Evasion* / immunology
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H1N1 Subtype / metabolism
  • Influenza Vaccines / immunology
  • Madin Darby Canine Kidney Cells
  • Protein Processing, Post-Translational / physiology

Substances

  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines

Grants and funding

All work funded directly by US gov′t. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.