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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.
Pubmed ID: 28594325 RIS Download
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View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U-937 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets RIG-I
View all literature mentionsThis unknown targets Human MAVS
View all literature mentionsThis monoclonal targets Ubiquitin, Lys63-Specific
View all literature mentionsThis monoclonal targets Ubiquitin, Lys48-Specific
View all literature mentionsThis polyclonal targets TRIM25
View all literature mentionsThis monoclonal targets VDAC1 / Porin
View all literature mentionsThis monoclonal targets MDA-5 (D74E4) Rabbit mAb
View all literature mentionsThis monoclonal targets Rig-I
View all literature mentionsThis monoclonal targets Phospho-I B (Ser32)
View all literature mentionsThis monoclonal targets IkappaB-alpha
View all literature mentionsThis monoclonal targets Phospho-IKKα/β (Ser176/180)
View all literature mentionsThis polyclonal targets IKKalpha
View all literature mentionsThis monoclonal targets NF-KappaB p65, phospho (Ser536)
View all literature mentionsThis unknown targets
View all literature mentionsThis monoclonal targets Phospho-IRF-3 (Ser396)
View all literature mentionsThis monoclonal targets SIGMAR1
View all literature mentionsThis polyclonal targets MAVS
View all literature mentionsThis polyclonal targets GAPDH
View all literature mentionsThis polyclonal targets ACTG1, ACTC1, ACTA1, ACTA2, ACTG2, ACTB
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis unknown targets c-Myc
View all literature mentionsThis monoclonal targets SIGMAR1
View all literature mentionsThis polyclonal targets GAPDH
View all literature mentionsThis unknown targets
View all literature mentionsThis unknown targets c-Myc
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis polyclonal targets ACTG1, ACTC1, ACTA1, ACTA2, ACTG2, ACTB
View all literature mentionsThis polyclonal targets IKKalpha
View all literature mentionsThis monoclonal targets IkappaB-alpha
View all literature mentionsThis monoclonal targets NF-KappaB p65, phospho (Ser536)
View all literature mentionsThis monoclonal targets Phospho-IKKα/β (Ser176/180)
View all literature mentionsThis monoclonal targets Phospho-I B (Ser32)
View all literature mentionsThis monoclonal targets Phospho-IRF-3 (Ser396)
View all literature mentionsThis polyclonal targets MAVS
View all literature mentionsThis monoclonal targets RIG-I
View all literature mentionsThis unknown targets Human MAVS
View all literature mentionsThis monoclonal targets Ubiquitin, Lys63-Specific
View all literature mentionsThis monoclonal targets Ubiquitin, Lys48-Specific
View all literature mentionsThis monoclonal targets MDA-5 (D74E4) Rabbit mAb
View all literature mentionsThis polyclonal targets TRIM25
View all literature mentionsThis monoclonal targets Rig-I
View all literature mentionsThis monoclonal targets VDAC1 / Porin
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