title: ECSIT bridges RIG-I-like receptors to VISA in signaling events of innate antiviral responses.
abstract: Upon binding to RNA structures from invading viruses, RIG-I and MDA5 are recruited to mitochondria to interact with VISA and initiate antiviral type I interferon (IFN) responses. How this process is mediated is less understood. In this report, we demonstrate that ECSIT is an essential scaffolding protein that mediates the association of VISA and RIG-I or MDA5. Overexpression of ECSIT potentiated virus-triggered activation of IFN-regulatory factor 3 (IRF3) and expression of IFNB1, whereas knockdown of ECSIT impaired viral infection-induced activation of IRF3 and expression of IFNB1 as well as cellular antiviral responses. Mechanistically, ECSIT was associated with VISA on mitochondria and important for bridging RIG-I and MDA5 to VISA. Our findings suggest that ECSIT mediates virus-triggered type I IFN induction by bridging RIG-I and MDA5 to the VISA complex, and provide new insights into the molecular events of innate antiviral immune responses.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Medical Research Institute, Wuhan University, Wuhan, China.
authors.forename: Cao-Qi
authors.initials: CQ
authors.lastname: Lei
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mi
authors.initials: M
authors.lastname: Li
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Jiang
authors.forename: Bo
authors.initials: B
authors.lastname: Zhong
authors.forename: Yong Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Shu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000956:Antigens, Viral / Q000276:immunology; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism; D000072640:Interferon-Induced Helicase, IFIH1; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D011971:Receptors, Immunologic; D015398:Signal Transduction / Q000235:genetics; D019076:Transgenes / Q000235:genetics; D014777:Virus Diseases / Q000276:immunology*; D014780:Viruses / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000956:Antigens, Viral; C518657:Ecsit protein, human; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C505371:MAVS protein, human; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D016899:Interferon-beta; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1