77 Scopus citations

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.

Original languageEnglish
Article numbere24425
JournaleLife
Volume6
DOIs
StatePublished - Jun 8 2017

Keywords

  • Adaptor Proteins, Signal Transducing/metabolism
  • Animals
  • Antiviral Agents/metabolism
  • Cell Line
  • Cyclophilin A/metabolism
  • DEAD Box Protein 58/metabolism
  • Humans
  • Interferon Type I/metabolism
  • Mice
  • Receptors, Immunologic
  • Sendai virus/immunology
  • Transcription Factors/metabolism
  • Tripartite Motif Proteins/metabolism
  • Ubiquitin-Protein Ligases/metabolism
  • Ubiquitination

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