The role of IRF1 in positive feedback of type I IFN transcription to combat Siniperca chuatsi rhabdovirus (SCRV) infection in teleost fish.

Abstract

Interferon regulatory factors (IRFs) play essential roles in virus-induced immune activation and IFN production, and IRF1 is involved in regulating diverse physiological processes, such as antiviral response; however, the molecular mechanism underlying its antiviral activity remains incompletely understood particularly in lower vertebrates such as teleost fish. In this study, IRF1 was found markedly upregulated following SCRV and type I IFN stimulation in MFF-1 cells. Ectopic expression of IRF1 robustly activated the transcription of type I IFNs, essential genes in IFN signaling pathways, and multiple IFN-stimulated genes (ISGs). This activation conferred strong antiviral protection, attenuating SCRV-induced cytopathic effects, reducing viral titers, and suppressing viral gene expression, including SCRV N, P, G, M, and L. Furthermore, dual-Luciferase reporter assay showed that promoters of type I IFNs, ISRE, Mx and IFP35 can all be induced following IRF1 overexpression. Taken together, IRF1 was found to initiate directly the intracellular innate immune transcription of type I IFNs, which is then amplified intercellularly through type I IFN and IRF3-mediated secretory pathway.