Pellino3 ligase negatively regulates Influenza B dependent RIG-I signaling through downregulation of TRAF3 mediated induction of the transcription factor IRF3 and IFNβ production.

Viral infection activates the innate immune system, which recognizes viral components by a variety of pattern recognition receptors and initiates signaling cascades leading to the production of pro-inflammatory cytokines. To date, signaling cascades triggered after virus recognition are not fully characterized and are investigated by many research groups. The critical role of the E3 ubiquitin ligase Pellino3 in antibacterial and antiviral response is now widely accepted, but the precise mechanism remains elusive. In this study, we sought to explore Pellino3 role in the RIG-I-dependent signaling pathway. In this work, the molecular mechanisms of the innate immune response, regulated by Pellino3, were investigated in lung epithelial cells during influenza B virus infection. We used wildtype and Pellino3-deficient A549 cells as model cell lines to examine the role of Pellino3 ligase in the type I IFN signaling pathway. Our results indicate that Pellino3 is involved in direct ubiquitination and degradation of the TRAF3, suppressing IRF3 activation and IFNβ production. This article is protected by copyright. All rights reserved.