Cyprinid Herpesvirus 2 Infection Activates IL-17C/NF-κB/IFNγ Antiviral Signalling Axis in Caudal Fin Cells of Carassius auratus Gibelio.

Abstract

Crucian carp (Carassius auratus gibelio) is sensitive to the infection of Cyprinid herpesvirus 2 (CyHV-2), displaying severe inflammatory reactions characterised by systemic congestion and gill bleeding. This study aimed to elucidate the mechanism by which CyHV-2 infection induces interferon gamma (IFNγ) expression in caudal fin cells (GiCF) of Carassius auratus gibelio, specifically investigating the role of the IL-17C/NF-κB signalling axis. In mammalian systems, virus-induced IL-17 has been demonstrated to activate NF-κB, a master regulator of inflammatory responses that controls multiple antiviral immune genes including interferons. Therefore, the induction mechanism of IFNγ gene expression following CyHV-2 infection was elucidated by revealing the interplay among IL-17C, NF-κB and IFNγ in this study. We demonstrated that CyHV-2 infection significantly upregulated the expression of IL-17C, NF-κB and IFNγ at both transcriptional and translational levels in GiCF. Furthermore, overexpression of IL-17C upregulated NF-κB and IFNγ expressions, while pharmacological inhibition of NF-κB (BAY 11-7082) suppressed this upregulation. This study provides the first evidence for the activation of IL-17C/NF-κB/IFNγ antiviral signalling axis in teleost fish in response to herpesvirus infection. Our findings highlight the dual role of virus-induced NF-κB activity, which not only orchestrates host defence (via IFNγ) but may also be exploited by the virus to potentially regulate its own gene transcription.