Interferon induction and/or production and its suppression by influenza A viruses

J Virol. 2005 Mar;79(5):2880-90. doi: 10.1128/JVI.79.5.2880-2890.2005.

Abstract

Developmentally aged chicken embryo cells which hyperproduce interferon (IFN) when induced were used to quantify IFN production and its suppression by eight strains of type A influenza viruses (AIV). Over 90% of the IFN-inducing or IFN induction-suppressing activity of AIV populations resided in noninfectious particles. The IFN-inducer moiety of AIV appears to preexist in, or be generated by, virions termed IFN-inducing particles (IFP) and was detectable under conditions in which a single molecule of double-stranded RNA introduced into a cell via endocytosis induced IFN, whereas single-stranded RNA did not. Some AIV strains suppressed IFN production, an activity that resided in a noninfectious virion termed an IFN induction-suppressing particle (ISP). The ISP phenotype was dominant over the IFP phenotype. Strains of AIV varied 100-fold in their capacity to induce IFN. AIV genetically compromised in NS1 expression induced about 20 times more IFN than NS1-competent parental strains. UV irradiation further enhanced the IFN-inducing capacity of AIV up to 100-fold, converting ISP into IFP and IFP into more efficient IFP. AIV is known to prevent IFN induction and/or production by expressing NS1 from a small UV target (gene NS). Evidence is presented for an additional downregulator of IFN production, identified as a large UV target postulated to consist of AIV polymerase genes PB1 + PB2 + PA, through the ensuing action of their cap-snatching endonuclease on pre-IFN-mRNA. The products of both the small and large UV targets act in concert to regulate IFN induction and/or production. Knowledge of the IFP/ISP phenotype may be useful in the development of attenuated AIV strains that maximally induce cytokines favorable to the immune response.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Chick Embryo
  • Dose-Response Relationship, Radiation
  • Genome, Viral
  • Hot Temperature
  • Immune Tolerance
  • Influenza A virus / classification
  • Influenza A virus / genetics
  • Influenza A virus / immunology*
  • Influenza A virus / radiation effects
  • Interferons / biosynthesis*
  • Kinetics
  • Repressor Proteins / metabolism
  • Species Specificity
  • Ultraviolet Rays

Substances

  • Repressor Proteins
  • Interferons