SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex

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• 作者：Xiaojuan Chen (1)
  Xingxing Yang (1) (2)
  Yang Zheng (1)
  Yudong Yang (1)
  Yaling Xing (1)
  Zhongbin Chen (1) (2)
  
• 关键词：SARS coronavirus ; papain ; like protease ; interferon ; deubiquitinase ; STING ; TRAF3 ; TBK1 complex
• 刊名：Protein & Cell
• 出版年：2014
• 出版时间：May 2014
• 年：2014
• 卷：5
• 期：5
• 页码：369-381
• 全文大小：
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• 作者单位：Xiaojuan Chen (1)
  Xingxing Yang (1) (2)
  Yang Zheng (1)
  Yudong Yang (1)
  Yaling Xing (1)
  Zhongbin Chen (1) (2)
  
  1. Division of Infection and Immunity, Department of Electromagnetic and Laser Biology, Beijing Institute of Radiation Medicine, Beijing, 100850, China
  2. Anhui Medical University, Hefei, 230032, China
  
• ISSN：1674-8018

文摘

SARS coronavirus (SARS-CoV) develops an antagonistic mechanism by which to evade the antiviral activities of interferon (IFN). Previous studies suggested that SARS-CoV papain-like protease (PLpro) inhibits activation of the IRF3 pathway, which would normally elicit a robust IFN response, but the mechanism(s) used by SARS PLpro to inhibit activation of the IRF3 pathway is not fully known. In this study, we uncovered a novel mechanism that may explain how SARS PLpro efficiently inhibits activation of the IRF3 pathway. We found that expression of the membrane-anchored PLpro domain (PLpro-TM) from SARS-CoV inhibits STING/TBK1/IKKε-mediated activation of type I IFNs and disrupts the phosphorylation and dimerization of IRF3, which are activated by STING and TBK1. Meanwhile, we showed that PLpro-TM physically interacts with TRAF3, TBK1, IKKε, STING, and IRF3, the key components that assemble the STING-TRAF3-TBK1 complex for activation of IFN expression. However, the interaction between the components in STING-TRAF3-TBK1 complex is disrupted by PLpro-TM. Furthermore, SARS PLpro-TM reduces the levels of ubiquitinated forms of RIG-I, STING, TRAF3, TBK1, and IRF3 in the STING-TRAF3-TBK1 complex. These results collectively point to a new mechanism used by SARS-CoV through which PLpro negatively regulates IRF3 activation by interaction with STING-TRAF3-TBK1 complex, yielding a SARS-CoV countermeasure against host innate immunity.