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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Gene induction pathways mediated by distinct IRFs during viral infection
1Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan.
Abstract:
During viral infection, interferon-alpha/beta (IFN-alpha/beta) and many IFN-inducible genes are induced to elicit antiviral responses of the host. Using cells with a gene disruption(s) for the IRF family of transcription factors, we provide evidence that these genes, containing similar IRF-binding cis-elements, are classified into distinct groups, based on the gene induction pathway(s). The IFN-beta gene induction is dependent on either IRF-3 or IRF-7, whereas induction of the IFN-alpha gene family is IRF-7-dependent. On the other hand, ISG15, ISG54 and IP-10 are induced by either IRF-3 or IFN stimulated gene factor 3 (ISGF3). We also show that another group of genes is totally dependent on ISGF3. Thus, during viral infection, a given gene responds either directly to a virus or virus-induced IFN-alpha/beta or both through distinct pathways. The differential utilization of these induction pathways for these genes during viral infection may reflect their distinct functional roles in the efficient antiviral response.
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