Abstract
Retinoic acid-inducible gene I (RIG-I) plays a pivotal role in innate immune responses as an intracellular sensor of viral RNAs. Recognition of dsRNA by RIG-I activates downstream IFN-inducible molecules including IRF3, resulting in the induction of type I IFN. However, the mechanisms that participate in downstream events following activation of RIG-I are incompletely understood. The objective of this study was to identify proteins that associated with RIG-I. Studies combining immunoprecipitation and mass spectrometry showed that RIG-I formed part of a protein complex that included heat shock protein 90 (HSP90), a molecular chaperone. Treatment with geldanamycin, a HSP90 inhibitor, dissociated the RIG-I: HSP90 complex and also resulted in the degradation of RIG-I protein. In contrast, the levels of RIG-I mRNA were not affected. In addition, the proteasomal inhibitor MG-132 significantly abolished geldanamycin-mediated RIG-I degradation, suggesting that HSP90 protected RIG-I from proteasomal degradation. Our results also showed that pretreatment with geldanamycin significantly reduced RIG-I mediated IFN-β promoter activity induced by polyinosinic: polycytidylic acid. Taken together, these data suggest that HSP90 plays a role in innate immune responses by shielding RIG-I from proteasomal degradation.
