vaccinia virus protein c6 is a virulence factor that binds tbk-1 adaptor proteins and inhibits activation of irf3 and irf7牛痘病毒蛋白质c6毒性因子,结合tbk-1适配器蛋白质和抑制irf3和irf7的激活.pdfVIP

Vaccinia Virus Protein C6 Is a Virulence Factor that Binds TBK-1 Adaptor Proteins and Inhibits Activation of IRF3 and IRF7 1. 2. 1 2 2 Leonie Unterholzner , Rebecca P. Sumner , Marcin Baran , Hongwei Ren , Daniel S. Mansur , 1 3 2 1 Nollaig M. Bourke , Felix Randow , Geoffrey L. Smith , Andrew G. Bowie * 1 School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland, 2 Department of Virology, Faculty of Medicine, Imperial College London, St Mary’s Campus, London, United Kingdom, 3 Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom Abstract Recognition of viruses by pattern recognition receptors (PRRs) causes interferon-b (IFN-b) induction, a key event in the anti- viral innate immune response, and also a target of viral immune evasion. Here the vaccinia virus (VACV) protein C6 is identified as an inhibitor of PRR-induced IFN-b expression by a functional screen of select VACV open reading frames expressed individually in mammalian cells. C6 is a member of a family of Bcl-2-like poxvirus proteins, many of which have been shown to inhibit innate immune signalling pathways. PRRs activate both NF-kB and IFN regulatory factors (IRFs) to activate the IFN-b promoter induction. Data presented here show that C6 inhibits IRF3 activation and translocation into the nucleus, but does not inhibit NF-kB activation. C6 inhibits IRF3 and IRF7 activation downstream of the kinases TANK binding kinase 1 (TBK1) and IkB kinase-e (IKKe), which phosphorylate and activate these IRFs. However, C6 doe