title: Induction of USP25 by viral infection promotes innate antiviral responses by mediating the stabilization of TRAF3 and TRAF6.
abstract: Host pathogen-recognition receptors detect nucleic acid from invading viruses and initiate a series of signaling pathways that lead to the production of type I interferons (IFNs) and proinflammatory cytokines. Here, we found that a viral infection-induced deubiquitinase (DUB), ubiquitin-specific protease 25 (USP25) was required for host defense against RNA and DNA viruses. The activation of transcription factors IRF3 and NF-κB was impaired and the production of type I IFNs and proinflammatory cytokines was inhibited in Usp25-/- cells compared with the wild-type counterparts after RNA or DNA viruses infection. Consistently, USP25 deficient mice were more susceptible to H5N1 or HSV-1 infection compared with the wild-type mice. USP25 was associated with TRAF3 and TRAF6 after infection by RNA or DNA viruses and protected virus-induced proteasome-dependent or independent degradation of TRAF3 and TRAF6, respectively. Moreover, reconstitution of TRAF3 and TRAF6 into Usp25-/- MEFs restored virus-triggered production of type I IFNs and proinflammatory cytokines. Our findings thus reveal a previously uncovered positive feedback regulation of innate immune responses against RNA and DNA viruses by USP25.
authors: Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060, China;
authors: Dandan
authors: D
authors: Lin
authors: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China;
authors: Man
authors: M
authors: Zhang
authors: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China;
authors: Meng-Xin
authors: MX
authors: Zhang
authors: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China;
authors: Yujie
authors: Y
authors: Ren
authors: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China;
authors: Jie
authors: J
authors: Jin
authors: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China;
authors: Quanyi
authors: Q
authors: Zhao
authors: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China;
authors: Zishu
authors: Z
authors: Pan
authors: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China;
authors: Min
authors: M
authors: Wu
authors: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China;
authors: Hong-Bing
authors: HB
authors: Shu
authors: School of Medicine, Tsinghua University, Beijing 10084, China.
authors: Chen
authors: C
authors: Dong
authors: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China; zhongbo@whu.edu.cn.
authors: Bo
authors: B
authors: Zhong
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015870:Gene Expression / Q000276:immunology; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D015151:Immunoblotting; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D048008:TNF Receptor-Associated Factor 3 / Q000276:immunology* / Q000378:metabolism; D048029:TNF Receptor-Associated Factor 6 / Q000276:immunology* / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology* / Q000821:virology; D014780:Viruses / Q000276:immunology*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D007370:Interferon Type I; D016328:NF-kappa B; D048008:TNF Receptor-Associated Factor 3; D048029:TNF Receptor-Associated Factor 6; C000603994:USP25 protein, mouse; D043222:Ubiquitin Thiolesterase; D046988:Proteasome Endopeptidase Complex
keywords: TRAF3; TRAF6; USP25; innate antiviral immunity