The microbiome regulates host metabolic health and diseases through microbial enzymes - Nature

We’re sharing this article early to provide faster access to peer-reviewed, accepted research. It is citable and carries a permanent DOI. This version is subject to further edits and will be replaced automatically by the final Version of Record. All legal disclaimers apply. AbstractThis study identifies TRIM2 as an interferon-stimulated gene (ISG) regulated by both type I and type II interferons. Contrary to the typical antiviral role of most ISGs, TRIM2 significantly enhances influenza A virus (IAV) replication both in vitro and in vivo. Mechanistically, TRIM2 functions as a negative regulator of the MDA5-mediated antiviral signaling pathway, contributing to the suppression of IFN-β production in part through promoting K48-linked polyubiquitination of MDA5. It directly interacts with MDA5 via its CC and Fn domains, promoting K48-linked polyubiquitination of MDA5 at Lysine 538, which leads to its proteasomal degradation and subsequent suppression of IFN-β production. Furthermore, TRIM2 interacts with and degrades STAT2 via K48-linked ubiquitination, further suppressing interferon signaling.