Abstract

SVCV infection upregulates hnRNPK and induces its nuclear-to-cytoplasmic translocation. • HnRNPK binds to and stabilizes the viral P protein, thereby enhancing viral replication. • hnRNPK promotes IRF3 degradation and blocks its nuclear entry, suppressing type I IFN responses. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a multifunctional RNA-binding protein implicated in various cellular processes, yet its role in fish antiviral immunity and viral replication remains poorly understood. In this study, we found that common carp ( Cyprinus carpio ) hnRNPK expression was markedly upregulated following SVCV infection or poly(I:C) stimulation, accompanied by its translocation from the nucleus to the cytoplasm. Overexpression of hnRNPK enhanced viral replication, as reflected by increased viral gene expression and viral titers. Mechanistically, hnRNPK interacted with the SVCV phosphoprotein (P) and promoted its stability. Additionally, hnRNPK suppressed type I interferon (IFN) production by interacting with key components of the RLR signaling pathway, including MITA, TBK1, IRF3, and IRF7. Notably, hnRNPK facilitated IRF3 degradation and impeded its nuclear translocation, thereby negatively regulating the type I IFN response. Collectively, these findings indicate that hnRNPK promotes SVCV replication through a dual mechanism: stabilizing the viral P protein and attenuating the host type I interferon response by targeting IRF3. This study provides new insights into the immune evasion strategies employed by SVCV and highlights hnRNPK as a potential target for antiviral intervention in lower vertebrates.