The soft palate is an important site of adaptation for transmissible influenza viruses

Nature. 2015 Oct 1;526(7571):122-5. doi: 10.1038/nature15379. Epub 2015 Sep 23.

Abstract

Influenza A viruses pose a major public health threat by causing seasonal epidemics and sporadic pandemics. Their epidemiological success relies on airborne transmission from person to person; however, the viral properties governing airborne transmission of influenza A viruses are complex. Influenza A virus infection is mediated via binding of the viral haemagglutinin (HA) to terminally attached α2,3 or α2,6 sialic acids on cell surface glycoproteins. Human influenza A viruses preferentially bind α2,6-linked sialic acids whereas avian influenza A viruses bind α2,3-linked sialic acids on complex glycans on airway epithelial cells. Historically, influenza A viruses with preferential association with α2,3-linked sialic acids have not been transmitted efficiently by the airborne route in ferrets. Here we observe efficient airborne transmission of a 2009 pandemic H1N1 (H1N1pdm) virus (A/California/07/2009) engineered to preferentially bind α2,3-linked sialic acids. Airborne transmission was associated with rapid selection of virus with a change at a single HA site that conferred binding to long-chain α2,6-linked sialic acids, without loss of α2,3-linked sialic acid binding. The transmissible virus emerged in experimentally infected ferrets within 24 hours after infection and was remarkably enriched in the soft palate, where long-chain α2,6-linked sialic acids predominate on the nasopharyngeal surface. Notably, presence of long-chain α2,6-linked sialic acids is conserved in ferret, pig and human soft palate. Using a loss-of-function approach with this one virus, we demonstrate that the ferret soft palate, a tissue not normally sampled in animal models of influenza, rapidly selects for transmissible influenza A viruses with human receptor (α2,6-linked sialic acids) preference.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological* / genetics
  • Animals
  • Epithelial Cells / metabolism
  • Epithelial Cells / virology
  • Female
  • Ferrets / virology
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism
  • Humans
  • Influenza A Virus, H1N1 Subtype / chemistry
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H1N1 Subtype / physiology*
  • Male
  • Molecular Sequence Data
  • Orthomyxoviridae Infections / transmission
  • Orthomyxoviridae Infections / virology
  • Palate, Soft / chemistry
  • Palate, Soft / metabolism*
  • Palate, Soft / virology*
  • Receptors, Virus / metabolism*
  • Respiratory System / cytology
  • Respiratory System / metabolism
  • Respiratory System / virology
  • Selection, Genetic* / genetics
  • Sialic Acids / chemistry
  • Sialic Acids / metabolism
  • Swine / virology

Substances

  • Hemagglutinin Glycoproteins, Influenza Virus
  • Receptors, Virus
  • Sialic Acids

Associated data

  • GENBANK/CY184674
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