Cyclophilin A-regulated ubiquitination is critical for RIG-I-mediated antiviral immune responses

• DOI: 10.7554/elife.24425
• Publication Date: 2017-06-08T12:00:16Z
• Authors: Wei Liu; Jing Li; Weinan Zheng; Yingli Shang; Zhendong Zhao; Shanshan Wang; Yuhai Bi; Shuang Zhang; Chongfeng Xu; Ziyuan Duan; Lianfeng Zhang; Yue L Wang; Zhengfan Jiang; Wenjun Liu; Lei Sun
• Keywords: Cypa; RIG-I; IRF3; MDA5; Sendai virus; Cyclophilin

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 cyclophilin A (CypA), peptidyl-prolyl cis/trans isomerase, functioned as critical positive regulator of RIG-I-mediated antiviral immune responses. Deficiency CypA impaired IFN production and promoted viral replication in human cells mice. Upon Sendai infection, increased the interaction between its E3 ubiquitin ligase TRIM25, leading enhanced TRIM25-mediated K63-linked ubiquitination facilitated recruitment MAVS. addition, TRIM25 competitively interacted MAVS, thereby inhibiting TRIM25-induced K48-linked Taken together, our findings reveal an essential role boosting responses by controlling