title: A novel viral SOCS from infectious spleen and kidney necrosis virus: interacts with Jak1 and inhibits IFN-α induced Stat1/3 activation.
abstract: Interferon (IFN)-induced Janus kinase (Jak)/signal transducer and activator of transcription (Stat) pathway is important in controlling immune responses and is negatively response-regulated by the suppressor of cytokine signaling (SOCS) proteins. However, several viruses have developed various strategies to inhibit this pathway to circumvent the anti-viral immunity of the host. The infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus in the family Iridoviridae and a causative agent of epizootics in fish. ISKNV ORF103R encodes a predicted viral SOCS (vSOCS) with high homology to the vertebrate SOCS1, but lacks a SOCS-box domain. Interestingly, vSOCS only exists in the genus Megalocytivirus. ISKNV-vSOCS can block the IFN-α-induced Jak/Stat pathway in HepG2 cells. Over-expression of ISKNV-vSOCS inhibited the activities of IFN-stimulated response element (ISRE) promoter; however, the inhibitions by ISKNV-vSOCS were dose-dependent. ISKNV-vSOCS interacted with Jak1 protein and inhibited its tyrosine kinase activity in vitro. ISKNV-vSOCS also impaired the phosphorylation of Stat1 and Stat3 proteins and suppressed their activations. The point mutations (F18D, S66A, S85A, and R64K) of ISKNV-vSOCS significantly impaired the inhibition of IFN-α-induced ISRE-promoter activation. In conclusion, vSOCS inhibits IFN-α-induced Stat1/Stat3 signaling, suggesting that Megalocytivirus has developed a novel strategy to evade IFN anti-viral immunity via vSOCS protein.
authors: MOE Key Laboratory of Aquatic Product Safety, School of Marine Science, Sun Yat-sen University, Guangzhou, PR China.
authors: Chang-Jun
authors: CJ
authors: Guo
authors: Li-Shi
authors: LS
authors: Yang
authors: Ying-Fen
authors: YF
authors: Zhang
authors: Yan-Yan
authors: YY
authors: Wu
authors: Shao-Ping
authors: SP
authors: Weng
authors: Xiao-Qiang
authors: XQ
authors: Yu
authors: Jian-Guo
authors: JG
authors: He
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology; D017930:Genes, Reporter / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D053613:Janus Kinase 1 / Q000378:metabolism*; D007668:Kidney / Q000821:virology*; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000187:drug effects; D017354:Point Mutation; D011485:Protein Binding; D050791:STAT Transcription Factors / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D050826:Suppressor of Cytokine Signaling Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053079:Trager duck spleen necrosis virus; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D016898:Interferon-alpha; D050791:STAT Transcription Factors; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050826:Suppressor of Cytokine Signaling Proteins; D014764:Viral Proteins; D053613:Janus Kinase 1