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10.1371/journal.ppat.1007067

http://scihub22266oqcxt.onion/10.1371/journal.ppat.1007067
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suck abstract from ncbi


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pmid29734366
      PLoS+Pathog 2018 ; 14 (5 ): e1007067
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  • Induction of OTUD1 by RNA viruses potently inhibits innate immune responses by promoting degradation of the MAVS/TRAF3/TRAF6 signalosome #MMPMID29734366
  • Zhang L ; Liu J ; Qian L ; Feng Q ; Wang X ; Yuan Y ; Zuo Y ; Cheng Q ; Miao Y ; Guo T ; Zheng X ; Zheng H
  • PLoS Pathog 2018[May]; 14 (5 ): e1007067 PMID29734366 show ga
  • During RNA virus infection, the adaptor protein MAVS recruits TRAF3 and TRAF6 to form a signalosome, which is critical to induce the production of type I interferons (IFNs) and proinflammatory cytokines. While activation of the MAVS/TRAF3/TRAF6 signalosome is well studied, the negative regulation of the signalosome remains largely unknown. Here we report that RNA viruses specifically promote the deubiquitinase OTUD1 expression by NF-?B-dependent mechanisms at the early stage of viral infection. Furthermore, OTUD1 upregulates protein levels of intracellular Smurf1 by removing Smurf1 ubiquitination. Importantly, RNA virus infection promotes the binding of Smurf1 to MAVS, TRAF3 and TRAF6, which leads to ubiquitination-dependent degradation of every component of the MAVS/TRAF3/TRAF6 signalosome and subsequent potent inhibition of IFNs production. Consistently, OTUD1-deficient mice produce more antiviral cytokines and are more resistant to RNA virus infection. Our findings reveal a novel immune evasion mechanism exploited by RNA viruses, and elucidate a negative feedback loop of MAVS/TRAF3/TRAF6 signaling mediated by the OTUD1-Smurf1 axis during RNA virus infection.
  • |Adaptor Proteins, Signal Transducing/*metabolism [MESH]
  • |Animals [MESH]
  • |Gene Knockdown Techniques [MESH]
  • |HEK293 Cells [MESH]
  • |Humans [MESH]
  • |Immunity, Innate/*immunology [MESH]
  • |Interferon Type I/genetics/metabolism [MESH]
  • |Interferon-beta/genetics/metabolism [MESH]
  • |Mice [MESH]
  • |RNA Virus Infections/immunology/prevention & control [MESH]
  • |RNA Viruses/*physiology [MESH]
  • |RNA, Messenger/metabolism [MESH]
  • |Signal Transduction [MESH]
  • |TNF Receptor-Associated Factor 3/*metabolism [MESH]
  • |TNF Receptor-Associated Factor 6/*metabolism [MESH]


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