Cyclophilin A-regulated ubiquitination is critical for RIG-I-mediated antiviral immune responses.
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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Antiviral Agents, Cell Line, Cyclophilin A, DEAD Box Protein 58, Humans, Interferon Type I, Mice, Sendai virus, Transcription Factors, Tripartite Motif Proteins, Ubiquitin-Protein Ligases, Ubiquitination
Adaptor Proteins, Signal Transducing, Animals, Antiviral Agents, Cell Line, Cyclophilin A, DEAD Box Protein 58, Humans, Interferon Type I, Mice, Sendai virus, Transcription Factors, Tripartite Motif Proteins, Ubiquitin-Protein Ligases, Ubiquitination
Elife
Date: Dec. 08, 2016
PubMed ID: 28594325
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