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论文题目: Cyclophilin A-regulated ubiquitination is critical for RIG-I-mediated antiviral immune responses
作者: Liu Wei , Li Jing , Zheng Weinan , Shang Yingli , Zhao Zhendong , Wang Shanshan , Bi Yuhai , Zhang Shuang, Xu Chongfeng , Duan Ziyuan , Zhang Lianfeng , Wang Yue L. , Jiang Zhengfan , Liu Wenjun*, and Sun Lei*.
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刊物名称: Elife
期: 6
卷:
页:
年份: 2017
影响因子: 8.385
论文下载: 下载地址
摘要: RIG-I is a key cytosolic pattern recognition receptor that interacts with MAVS to induce type I interferons (IFNs) against RNA virus infection. In this study, we found that cyclophilin A (CypA), a peptidyl-prolyl cis/trans isomerase, functioned as a critical positive regulator of RIG-I mediated antiviral immune responses. Deficiency of CypA impaired RIG-I-mediated type I IFN production and promoted viral replication in human cells and mice. Upon Sendai virus infection, CypA increased the interaction between RIG-I and its E3 ubiquitin ligase TRIM25, leading to enhanced TRIM25-mediated K63-linked ubiquitination of RIG-I that facilitated recruitment of RIG-I to MAVS. In addition, CypA and TRIM25 competitively interacted with MAVS, thereby inhibiting TRIM25-induced K48-linked ubiquitination of MAVS. Taken together, our findings reveal an essential role of CypA in boosting RIG-I-mediated antiviral immune responses by controlling the ubiquitination of RIG-I and MAVS.
   

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