Common carp Ftr82 positively regulates antiviral innate immunity by promoting Irf3 K63-linked ubiquitination

FinTRIM (FTR) proteins are a lineage-specific subfamily of TRIM E3 ubiquitin ligases in teleost fish and play important roles in antiviral innate immunity; however, the functions and underlying mechanisms of many FTR members remain poorly understood. In this study, we characterized a previously unappreciated FTR protein, CcFtr82, in common carp (Cyprinus carpio) and investigated its function in antiviral responses against spring viremia of carp virus (SVCV). We found that Ccftr82 expression was markedly induced by SVCV infection both in vivo and in vitro. Functional analyses revealed that overexpression of CcFtr82 significantly inhibited SVCV replication, whereas knockdown of endogenous ftr82 enhanced viral proliferation. Mechanistically, CcFtr82 positively regulated type I interferon (IFN-I) signaling by interacting with interferon regulatory factor 3 (Irf3) and promoting its K63-linked polyubiquitination. This modification facilitated Tbk1-Irf3 complex formation, enhanced Irf3-mediated antiviral signaling, and led to increased expression of ifnφ1 and interferon-stimulated genes (ISGs). Collectively, our findings identify CcFtr82 as a novel positive regulator of Irf3-dependent antiviral innate immunity and expand the functional understanding of finTrim proteins in teleost fish, providing new insights into host defense mechanisms against viral infection.