title: Negative regulation of Nmi on virus-triggered type I IFN production by targeting IRF7.
abstract: Viral infection causes host cells to produce type I IFNs, which play a critical role in viral clearance. IFN regulatory factor (IRF) 7 is the master regulator of type I IFN-dependent immune responses. In this article, we report that N-Myc and STATs interactor (Nmi), a Sendai virus-inducible protein, interacted with IRF7 and inhibited virus-triggered type I IFN production. The overexpression of Nmi inhibited the Sendai virus-triggered induction of type I IFNs, whereas the knockdown of Nmi promoted IFN production. Furthermore, the enhanced production of IFNs resulting from Nmi knockdown was sufficient to protect cells from infection by vesicular stomatitis virus. In addition, Nmi was found to promote the K48-linked ubiquitination of IRF7 and the proteasome-dependent degradation of this protein. Finally, an impairment of antiviral responses is also detectable in Nmi-transgenic mice. These findings suggest that Nmi is a negative regulator of the virus-triggered induction of type I IFNs that targets IRF7.
authors: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People's Republic of China.
authors: Jie
authors: J
authors: Wang
authors: Bo
authors: B
authors: Yang
authors: Yu
authors: Y
authors: Hu
authors: Yuhan
authors: Y
authors: Zheng
authors: Haiyan
authors: H
authors: Zhou
authors: Yanming
authors: Y
authors: Wang
authors: Yonglei
authors: Y
authors: Ma
authors: Kairui
authors: K
authors: Mao
authors: Leilei
authors: L
authors: Yang
authors: Guomei
authors: G
authors: Lin
authors: Yongyong
authors: Y
authors: Ji
authors: Xiaodong
authors: X
authors: Wu
authors: Bing
authors: B
authors: Sun
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D050839:Interferon Regulatory Factor-7 / Q000276:immunology / Q000378:metabolism*; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D060888:Real-Time Polymerase Chain Reaction; D010253:Respirovirus Infections / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029082:Sendai virus / Q000276:immunology; D014162:Transfection
chemical_list: D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; D047908:Intracellular Signaling Peptides and Proteins; C494235:Irf7 protein, mouse