Epigoitrin Exerts in vitro anti-MRV Effect via Activation of Interferon-Stimulated Genes

Abstract

The mandarin fish ranavirus (MRV), classified within the genus Ranavirus of the Iridoviridae family, is a lethal pathogen to Mandarin fish (Siniperca chuatsi). ​Currently, no approved treatment exists, underscoring the urgent need for therapeutic strategies. ​In this study, we aimed to investigate the antiviral activity of epigoitrin against MRV. ​An in vitro antiviral activity assay revealed that the CC₅₀ of epigoitrin is 43.16 μM, as determined by the CCK-8 assay. ​Epigoitrin effectively reduced the number of MRV copies from 8.63 × 10⁸ copies/mL to 1.82 × 10⁸ copies/mL, exhibiting dose-dependent inhibition of MRV replication. ​The effective concentration (EC₅₀) of epigoitrin was further determined to be 13.72 μM. ​Moreover, epigoitrin diminished the MRV-induced cytopathic effect as observed under a light microscope and suppressed the expression of major caspid protein of MRV (MRV-MCP), as visualized by immunofluorescence assay. ​It was revealed that epigoitrin primarily exerts its antiviral effects during the stage of viral replication. ​Further investigation into the immune response revealed that epigoitrin significantly upregulated the gene expression of Mx1 (5-fold), IFITM (2.5-fold), viperin (10-fold), ISG15 (15-fold), and IRF5 (2-fold). ​This suggests that epigoitrin indirectly unleashes its antiviral function by activating the host's interferon (IFN) immune response. ​In conclusion, our findings indicate that epigoitrin holds great potential as a therapeutic agent against MRV infection by modulating the IFN pathway.