Neutralizing inhibitors in the airways of naïve ferrets do not play a major role in modulating the virulence of H3 subtype influenza A viruses

Virology. 2016 Jul:494:143-57. doi: 10.1016/j.virol.2016.01.024. Epub 2016 Apr 26.

Abstract

Many insights regarding the pathogenesis of human influenza A virus (IAV) infections have come from studies in mice and ferrets. Surfactant protein (SP)-D is the major neutralizing inhibitor of IAV in mouse airway fluids and SP-D-resistant IAV mutants show enhanced virus replication and virulence in mice. Herein, we demonstrate that sialylated glycoproteins, rather than SP-D, represent the major neutralizing inhibitors against H3 subtype viruses in airway fluids from naïve ferrets. Moreover, while resistance to neutralizing inhibitors is a critical factor in modulating virus replication and disease in the mouse model, it does not appear to be so in the ferret model, as H3 mutants resistant to either SP-D or sialylated glycoproteins in ferret airway fluids did not show enhanced virulence in ferrets. These data have important implications for our understanding of pathogenesis and immunity to human IAV infections in these two widely used animal models of infection.

Keywords: Animal model; Influenza; Innate; Lectin; Surfactant; Virulence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Ferrets
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism
  • Host-Pathogen Interactions* / immunology
  • Humans
  • Immunity, Innate
  • Influenza A virus / classification
  • Influenza A virus / pathogenicity
  • Influenza A virus / physiology*
  • Male
  • Mice
  • Mutation
  • Neutralization Tests
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / pathology
  • Orthomyxoviridae Infections / virology*
  • Pulmonary Surfactant-Associated Protein D / metabolism
  • Respiratory System / immunology
  • Respiratory System / metabolism
  • Respiratory System / pathology
  • Respiratory System / virology
  • Virulence / genetics

Substances

  • Hemagglutinin Glycoproteins, Influenza Virus
  • Pulmonary Surfactant-Associated Protein D