Published June 8, 2017
| Version v1
Journal article
Open
Cyclophilin A-regulated ubiquitination is critical for RIG-I-mediated antiviral immune responses
Creators
- 1. Chinese Academy of Sciences
- 2. Shandong Agricultural University
- 3. Peking University
- 4. University of Chicago
Description
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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Additional details
Identifiers
- DOI
- 10.7554/eLife.24425
- Other
- oai:uchicago.tind.io:9953
Funding
- National Natural Science Foundation of China
- 31472178
- National Natural Science Foundation of China
- 31672531
- Chinese Academy of Sciences
- Key Research Program
- National Natural Science Foundation of China
- 31630079
- National Key Technology Support Program of China
- 2015BAD11B02
- National Natural Science Foundation of China
- 81621091