Mammalian adaptation of influenza A(H7N9) virus is limited by a narrow genetic bottleneck

Nat Commun. 2015 Apr 8;6:6553. doi: 10.1038/ncomms7553.

Abstract

Human infection with avian influenza A(H7N9) virus is associated mainly with the exposure to infected poultry. The factors that allow interspecies transmission but limit human-to-human transmission are unknown. Here we show that A/Anhui/1/2013(H7N9) influenza virus infection of chickens (natural hosts) is asymptomatic and that it generates a high genetic diversity. In contrast, diversity is tightly restricted in infected ferrets, limiting further adaptation to a fully transmissible form. Airborne transmission in ferrets is accompanied by the mutations in PB1, NP and NA genes that reduce viral polymerase and neuraminidase activity. Therefore, while A(H7N9) virus can infect mammals, further adaptation appears to incur a fitness cost. Our results reveal that a tight genetic bottleneck during avian-to-mammalian transmission is a limiting factor in A(H7N9) influenza virus adaptation to mammals. This previously unrecognized biological mechanism limiting species jumps provides a measure of adaptive potential and may serve as a risk assessment tool for pandemic preparedness.

Publication types

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

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Asymptomatic Infections
  • Chickens
  • Chlorocebus aethiops
  • Dogs
  • Ferrets
  • Genetic Variation*
  • HEK293 Cells
  • Humans
  • Influenza A Virus, H7N9 Subtype / genetics*
  • Influenza A Virus, H7N9 Subtype / pathogenicity
  • Influenza in Birds / transmission
  • Influenza in Birds / virology*
  • Influenza, Human
  • Madin Darby Canine Kidney Cells
  • Multiplex Polymerase Chain Reaction
  • Mutation
  • Neuraminidase / genetics
  • Orthomyxoviridae Infections / transmission
  • Orthomyxoviridae Infections / virology*
  • RNA, Viral / genetics*
  • RNA-Binding Proteins / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vero Cells
  • Viral Core Proteins / genetics
  • Viral Proteins / genetics

Substances

  • NP protein, Influenza A virus
  • RNA, Viral
  • RNA-Binding Proteins
  • Viral Core Proteins
  • Viral Proteins
  • influenza virus polymerase basic protein 1
  • NA protein, influenza A virus
  • Neuraminidase