title: An autoinhibitory mechanism modulates MAVS activity in antiviral innate immune response.
abstract: In response to virus infection, RIG-I senses viral RNA and activates the adaptor protein MAVS, which then forms prion-like filaments and stimulates a specific signalling pathway leading to type I interferon production to restrict virus proliferation. However, the mechanisms by which MAVS activity is regulated remain elusive. Here we identify distinct regions of MAVS responsible for activation of transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). These IRF3- and NF-κB-stimulating regions recruit preferential TNF receptor-associated factors (TRAFs) for downstream signalling. Strikingly, these regions' activities are inhibited by their respective adjacent regions in quiescent MAVS. Our data thus show that an autoinhibitory mechanism modulates MAVS activity in unstimulated cells and, on viral infection, individual regions of MAVS are released following MAVS filament formation to activate antiviral signalling cascades.
authors.affiliation: State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yuheng
authors.initials: Y
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Bofeng
authors.initials: B
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Jingru
authors.initials: J
authors.lastname: Su
authors.affiliation: State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Fajian
authors.initials: F
authors.lastname: Hou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000276:immunology*; D055786:Gene Knockout Techniques; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D050838:Interferon Regulatory Factor-3 / Q000276:immunology; D007370:Interferon Type I / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D012367:RNA, Viral / Q000276:immunology*; D011971:Receptors, Immunologic; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D018116:Vesiculovirus
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D016328:NF-kappa B; D012367:RNA, Viral; D011971:Receptors, Immunologic; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; C512612:MAVS protein, mouse; C505371:MAVS protein, human; C452820:RIGI protein, human; C503356:Ddx58 protein, mouse