Cyclophilin A-regulated ubiquitination is critical for RIG-I-mediated antiviral immune responses
- Chinese Academy of Sciences, China
- Shandong Agricultural University, China
- Chinese Academy of Medical Sciences, China
- University of Chicago, United States
- School of Life Sciences, Peking University, China
Abstract
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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Author details
Funding
National Natural Science Foundation of China (31472178)
- Lei Sun
National Natural Science Foundation of China (31672531)
- Lei Sun
Key Research Program of Chinese Academy of Sciences (KSZD-EW-Z-005-001)
- Wenjun Liu
National Key Technology Support Program of China (2015BAD11B02)
- Lei Sun
National Natural Science Foundation of China (81621091)
- Wenjun Liu
National Key Research and Development Program of China (2016YFC1201001)
- Lei Sun
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: The animal research was approved by the Research Ethics Committee of Chinese Academy of Sciences (Permit Number: PZIMCAS2013001), and complied with the Beijing Laboratory Animal Welfare and Ethical Guidelines of the Beijing Administration Committee of Laboratory Animals.
Copyright
© 2017, Liu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Cyclophilin A-regulated ubiquitination is critical for RIG-I-mediated antiviral immune responses
eLife 6:e24425.
https://doi.org/10.7554/eLife.24425
