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    Microbes Infect. 2006 Jul;8(8):2013-20. Epub 2006 May 22.

    Retinoic acid inducible gene-I and mda-5 are involved in influenza A virus-induced expression of antiviral cytokines.

    Sirén J, Imaizumi T, Sarkar D, Pietilä T, Noah DL, Lin R, Hiscott J, Krug RM, Fisher PB, Julkunen I, Matikainen S.

    Source

    Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland.

    Abstract

    Activation of host cell antiviral responses is mediated by pattern recognition receptors. Cytoplasmic RNA helicases, retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (mda-5) have been identified to function as receptors for double-stranded RNA. Here we show that interferon (IFN)-alpha pretreatment enhances influenza A virus-induced expression of IFN-alpha, IFN-beta, interleukin (IL)-28 and IL-29 genes in human dendritic cells and epithelial cell lines. Both IFN-alpha and IFN-beta strongly enhanced RIG-I and mda-5 mRNA and protein expression in these cell types. Expression of RIG-I and mda-5 gene constructs, but not that of TLR3, lead to a dramatic enhancement of IFN-beta promoter driven transcription in influenza A virus-infected epithelial cells. Furthermore, dominant negative RIG-I gene construct inhibited influenza A virus-induced IFN-beta promoter activity. In conclusion, our results show that in epithelial cells influenza A virus-induced antiviral cytokine gene expression is triggered by RIG-I and mda-5, whose expression is positively regulated by IFN-alpha.

    PMID:
    16797201
    [PubMed - indexed for MEDLINE]

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