SCRV-induced miR-365–3p inhibits viral replication by targeting OTUD7B-mediated autophagy in silver carp (Hypophthalmichthys molitrix)

The regulatory functions of microRNAs (miRNAs) in modulating viral pathogenesis have emerged as a pivotal research focus. Aquatic species, inhabiting ecologically distinct environments, exhibit heightened vulnerability to pathogenic challenges, posing substantial threats to global aquaculture productivity. Despite advancements in mammalian miRNA studies, mechanistic insights into piscine miRNA-mediated antiviral responses remain fragmented. Herein, we employed silver carp ( Hypophthalmichthys molitrix ) to delineate the role of miR-365–3p in SCRV pathogenesis. Experimental data demonstrated SCRV-induced transcriptional activation of miR-365–3p, which functioned as a viral restriction factor by attenuating SCRV replication and impeding infected cell proliferation. Mechanistically, integrative analyses combining dual-luciferase assays with multi-omics validation revealed OTUD7B as a direct functional target of miR-365–3p. Importantly, OTUD7B suppressed autophagy via the PI3K/AKT/mTOR pathway to promote viral replication. In contrast, miR-365–3p overexpression restored autophagic flux to counteract this effect. Collectively, our findings establish a novel miR-365–3p/OTUD7B regulatory network governing autophagic antiviral defense, advancing the understanding of teleost miRNA-mediated immunity and informing therapeutic strategies against aquatic viral diseases. • miR-365 targets and inhibits OTUD7B expression at both the mRNA and protein levels in silver carp. • miR-365 can be upregulated by SCRV stimulation and its overexpression inhibits virus replication. • miR-365 mitigate SCRV infection by targeting OTUD7B-mediated autophagy.