Genome editing of FTR100 generates two gibel carp mutants highly resistant to herpesvirus infection

Outbreaks of Carassius auratus herpesvirus (CaHV) remain a major constraint on the sustainable culture of gibel carp in China. CRISPR/Cas9-mediated genome editing offers a promising approach for improving disease resistance in aquaculture, but its application is limited by the lack of suitable target genes. Here, we report that FTR100, an Otomorpha-specific member of the fish novel TRIM (finTRIM/FTR) family, represents a potential target for antiviral breeding in gibel carp. Despite multiple rounds of whole-genome duplication (WGD), FTR100 is retained as a single-copy locus in all examined species, representing a distinct evolutionary lineage conserved within Otomorpha. Functionally, gibel carp FTR100 acted as a negative regulator of the interferon (IFN) response, mainly by promoting proteasome-dependent degradation of IFN regulatory factor 7 (IRF7). Using CRISPR/Cas9-mediated genome editing, we generated two FTR100-deficient gibel carp lines, both of which exhibited markedly enhanced resistance to CaHV infection, with survival rates increased by more than 80%. Importantly, the antiviral phenotype was stably inherited, and no obvious abnormalities were observed in growth and reproduction based on analyses of F1- and F2-generation mutant fish. Under uninfected conditions, FTR100-deficient fish exhibited moderately elevated basal expression of selected ISGs and enrichment of pathways related to immune regulation, cytokine signaling, and stimulus responses, suggesting that mutant fish acquire a sustained pre-activated antiviral state compared to wildtype fish. Collectively, these findings show that genome editing of FTR100 enhances antiviral resistance while maintaining key production traits, highlighting FTR100 as a promising molecular target for disease-resistance breeding in aquaculture species.