CcFTR54 restricts spring viremia of carp virus replication by promoting p62-mediated autophagic degradation of N protein.

Abstract

The tripartite motif (TRIM) protein family represents one of the largest groups of E3 ubiquitin ligases and plays pivotal roles in host antiviral innate immunity. In teleost fish, finTRIM proteins (FTR) have undergone lineage-specific expansion. However, the antiviral functions and molecular mechanisms of most FTR members remain largely unexplored. In this study, we identified a novel FTR protein from common carp (named CcFTR54) and demonstrated its critical antiviral role against spring viremia of carp virus (SVCV). It was found that CcFTR54 expression was markedly upregulated in immune-related tissues and peripheral blood leukocytes (PBLs) following SVCV infection. Functional analyses revealed that overexpression of CcFTR54 significantly suppressed SVCV replication in an interferon-independent manner. Mechanistically, CcFTR54 acted as an E3 ubiquitin ligase that promoted K48-linked ubiquitination of the N protein at K119, which strengthened the interaction between N protein and the autophagy receptor p62, thereby facilitating p62-mediated selective autophagic degradation of the N protein. Importantly, p62 knockdown attenuated CcFTR54-mediated N protein degradation and antiviral activity. Collectively, these findings uncover a novel finTRIM-mediated antiviral mechanism in teleost fish, providing new insights into host-virus interactions and potential strategies for the control viral diseases in aquaculture.