Human influenza viruses activate an interferon-independent transcription of cellular antiviral genes: outcome with influenza A virus is unique.
We examine the IFN-alpha/beta-independent activation of cellular transcription that constitutes an early antiviral response of cells against influenza A and B viruses, which cause widespread epidemics in humans. We show that influenza B virus induces the synthesis in human cells of several mature mRNAs encoded by genes containing an IFN-alpha/beta-stimulated response element (ISRE). Consequently, the IFN regulatory factor-3 transcription factor, which is required for the transcription of ISRE-controlled genes, is activated after influenza B virus infection. The production of these cellular mRNAs, some of which encode antiviral proteins, is independent of not only IFN-alpha/beta, but also viral protein synthesis. These mature cellular antiviral mRNAs are not produced after infection with influenza A virus, but IFN regulatory factor-3 is activated and the transcription of the ISRE-controlled p56 gene is induced. Consequently, like other newly synthesized cellular premRNAs in influenza A virus-infected cells, the posttranscriptional processing of premRNAs encoded by ISRE-controlled genes is inhibited. Previous work has established that such posttranscriptional inhibition is mediated by the viral NS1A protein. This unique, global countermeasure against the early, IFN-alpha/beta-independent antiviral response of cells may be an important factor in the pathogenicity of influenza A virus infection.
Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas, Austin, TX 78712, USA.
Mee-Jung
MJ
Kim
Anita Ghate
AG
Latham
Robert M
RM
Krug
D000998:Antiviral Agents / Q000378:metabolism*; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D006801:Humans; D009980:Influenza A virus / Q000276:immunology / Q000502:physiology*; D009981:Influenza B virus / Q000276:immunology / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics*; D014158:Transcription, Genetic
D000998:Antiviral Agents; D012333:RNA, Messenger