FTR33, a member of fish-specific TRIM (finTRIM) subfamily, regulates negatively type I IFN antiviral immunity in zebrafish

In mammals, the tripartite motif (TRIM) proteins have been identified as critical factors involved in various cellular processes, including antiviral immunity. In teleost fish, a subfamily of fish-specific TRIM (finTRIM, FTR) has emerged in genus- or species-specific duplication. In this study, a finTRIM gene, called ftr33, was identified in zebrafish (Danio rerio), and phylogenic analysis revealed that FTR33 is closely related with zebrafish FTR14. The FTR33 protein contains all conservative domains reported in other finTRIMs. The ftr33 has a constitutive expression in embryos and in tissues/organs of adult fish, and its expression can be induced following spring viremia of carp virus (SVCV) infection and interferon (IFN) stimulation. The overexpression of FTR33 significantly downregulated the expression of type I IFNs and IFN-stimulated genes (ISGs) both in vitro and in vivo, respectively, leading to the increased replication of SVCV. It was also found that FTR33 interacted with melanoma differentiation associated gene 5 (MDA5) or mitochondrial anti-viral signaling protein (MAVS) to weaken the promoter activity of type I IFN. It is thus concluded that the FTR33, as an ISG, in zebrafish can negatively regulate IFN-mediated antiviral response. •FTR33 gene, a member in fish-specific tripartite motif protein (finTRIM) subfamily was cloned in zebrafish.•The expression of ftr33 was induced in vivo following SVCV infection and IFN stimulation in vivo.•Overexpression of FTR33 resulted in reduced expression of type I IFNs and ISGs, but in increased virus proliferation.•FTR33 suppressed MDA5 and MAVS mediated type I IFN response.