A teleost NK-lysin derived peptide inhibits SVCV infection by disruption viral adhesion/entry and activating type I interferon response.

NK-lysin, a member of the saposin-like protein family, is a potent antimicrobial peptide that plays a key role in host defense against various pathogens. However, research on its antiviral activity and underlying mechanisms remains limited. In this study, the anti-SVCV activity and action mechanism of NKLj27, an NK-lysin derived peptide from Lateolabrax japonicus, were investigated primarily in EPC cells. Cytotoxicity assays revealed that NKLj27 was non-toxic to EPC cells at concentrations ranging from 5 μM to 160 μM. NKLj27 significantly inhibited SVCV infection in EPC cells, as demonstrated by marked reductions in viral infectivity, cytopathic effects, and plaque formation, together with decreased apoptosis and necrosis. Mechanistically, NKLj27 appears to exert its antiviral activity through a dual-target strategy, acting on both the viral particle and host cells. Further investigation revealed that NKLj27 interfered with the early stages of SVCV infection by inhibiting viral adhesion and cellular entry. Additionally, NKLj27 bound to and was partially internalized by EPC cells, and it also activated the type I interferon signaling, which was shown to play an important role in its antiviral activity through inhibition assays. Finally, in vivo experiments confirmed that administration of NKLj27 significantly reduced the mortality of SVCV-infected common carp and markedly decreased viral loads in the spleen, liver, and gill tissues. Collectively, these findings demonstrate that NKLj27 inhibits SVCV infection through a dual-target mechanism involving multiple pathways, highlighting its promising potential as a novel antiviral agent for application in aquaculture.