Influenza A virus PB1-F2 protein: An ambivalent innate immune modulator and virulence factor

J Leukoc Biol. 2020 May;107(5):763-771. doi: 10.1002/JLB.4MR0320-206R. Epub 2020 Apr 23.

Abstract

Influenza A virus (IAV) causes not only seasonal respiratory illness, but also outbreaks of more severe disease and pandemics when novel strains emerge as a result of reassortment or interspecies transmission. PB1-F2 is an IAV protein expressed from the second open reading frame of PB1 gene. Small as it is, PB1-F2 is a critical virulence factor. Multiple key amino acid residues and motifs of PB1-F2 have been shown to influence the virulence of IAV in a strain- and host-specific manner, plausibly through the induction of apoptotic cell death, modulation of type I IFN response, activation of inflammasome, and facilitation of secondary bacterial infection. However, the exact role of PB1-F2 in IAV pathogenesis remains unexplained. Through reanalysis of the current literature, we redefine PB1-F2 as an ambivalent innate immune modulator that determines IAV infection outcome through induction of immune cell death, differential modulation of early- and late-type I IFN response, and promotion of pathogenic inflammation. PB1-F2 functions both intracellularly and extracellularly. Further investigations of the mechanistic details of PB1-F2 action will shed new light on immunopathogenesis of IAV infection.

Keywords: avian influenza virus; inflammasome; inflammation; influenza A virus; innate antiviral response; type I IFNs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Immunity, Innate / immunology*
  • Influenza A virus / pathogenicity*
  • Influenza, Human / immunology*
  • Viral Proteins / immunology*
  • Virulence / immunology
  • Virulence Factors / immunology*

Substances

  • PB1-F2 protein, Influenza A virus
  • Viral Proteins
  • Virulence Factors