| First Author | Liu W | Year | 2017 |
| Journal | Elife | Volume | 6 |
| PubMed ID | 28594325 | Mgi Jnum | J:257113 |
| Mgi Id | MGI:6116940 | Doi | 10.7554/eLife.24425 |
| Citation | Liu W, et al. (2017) Cyclophilin A-regulated ubiquitination is critical for RIG-I-mediated antiviral immune responses. Elife 6:e24425 |
| abstractText | 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. |
