Single nucleoprotein residue determines influenza A virus sensitivity to an intertypic suppression mechanism

Virology. 2017 Jun:506:99-109. doi: 10.1016/j.virol.2017.03.015. Epub 2017 Mar 31.

Abstract

Several mechanisms underlying intertypic interference between co-infecting influenza types A and B viruses (IAV and IBV) have been proposed. We have recently described one in which IBV's nucleoprotein (BNP) sequestered IAV's nucleoprotein (ANP) and suppressed IAV polymerase and growth. However, its anti-IAV capacity and limitations have not been fully explored. Here, we showed that BNP's inhibitory effect was more potent toward a wide array of avian IAVs, whereas human IAVs revealed moderate resistance. BNP sensitivity was largely determined by ANP's residue 343 at the NP oligomerization interface. An avian IAV polymerase carrying an NP-V343L mutation switched from being highly BNP-sensitive to moderately BNP-resistant, and vice versa for a human IAV polymerase carrying a reverse mutation. To highlight its capacity, we demonstrated that the polymerases of highly-pathogenic H5N1 and the pandemic 2009 (H1N1) strains are strongly inhibited by BNP. Our work provides insights into lineage-specific sensitivity to BNP-mediated intertypic interference.

Keywords: Avian influenza virus; Influenza virus; Intertypic interference; Nucleoprotein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Birds
  • Humans
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H1N1 Subtype / physiology
  • Influenza A Virus, H3N2 Subtype / genetics
  • Influenza A Virus, H3N2 Subtype / physiology
  • Influenza A Virus, H5N1 Subtype / genetics
  • Influenza A Virus, H5N1 Subtype / physiology
  • Influenza A virus / genetics*
  • Influenza B virus / genetics*
  • Influenza B virus / physiology
  • Influenza in Birds / psychology*
  • Influenza in Birds / virology*
  • Influenza, Human / virology*
  • Mutation
  • Nucleoproteins / genetics*
  • Nucleoproteins / metabolism
  • Polymorphism, Single Nucleotide

Substances

  • Nucleoproteins