Residues in the PB2 and PA genes contribute to the pathogenicity of avian H7N3 influenza A virus in DBA/2 mice

Virology. 2016 Jul;494:89-99. doi: 10.1016/j.virol.2016.04.013. Epub 2016 Apr 20.

Abstract

Replication and transmission of avian influenza virus in humans poses a pandemic threat. The molecular determinants that facilitate this process are not well understood. We used DBA/2 mice to identify viral factors that mediate the difference in pathogenesis between a virulent (H7N3) and a non-virulent (H7N9) avian influenza virus from North America. In vitro and in vivo characterization of reassortant viruses identified the PB2 and PA polymerase genes as major determinants of H7N3 pathogenesis. Analysis of individual residues in the PB2 and PA genes identified position 358 (E358V) in PB2 and positions 190 (P190S) and 400 (Q400P) in PA that reduced the virulence of H7N3 virus. The E358V and P190S substitutions also caused reduced inflammation after infection. Our results suggest that specific residues in the polymerase proteins PB2 and PA are important for replication and virulence of avian influenza viruses in a mammalian host.

Keywords: Avian influenza virus; DBA/2J; H7 subtype; Pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Amino Acids
  • Animals
  • Conserved Sequence
  • Influenza A Virus, H7N3 Subtype / genetics*
  • Influenza A Virus, H7N3 Subtype / pathogenicity*
  • Influenza A Virus, H7N9 Subtype / genetics
  • Influenza A Virus, H7N9 Subtype / pathogenicity
  • Mice
  • Mice, Inbred DBA
  • Orthomyxoviridae Infections / mortality
  • Orthomyxoviridae Infections / virology*
  • RNA Replicase / chemistry
  • RNA Replicase / genetics*
  • Reassortant Viruses / genetics
  • Reassortant Viruses / pathogenicity
  • Severity of Illness Index
  • Viral Load
  • Viral Proteins / chemistry
  • Viral Proteins / genetics*
  • Virulence Factors / genetics
  • Virus Replication

Substances

  • Amino Acids
  • PA protein, influenza viruses
  • PB2 protein, Influenzavirus A
  • Viral Proteins
  • Virulence Factors
  • RNA Replicase