Identification of Fish Interferon Stimulated Genes and Their Antiviral Mechanisms

The frontlines of innate antiviral immunity center on type I interferons (IFN), which are expressed by nearly all cell types as a cellular alarm signal. IFNs drive the expression of IFN-stimulated genes (ISGs), which can both generate an intracellular antiviral state and regulate the IFN response itself. This key antiviral line of defense is con-served in all jawed vertebrates, including teleost fish. Since their identification nearly 70 years ago, many mammalian ISGs have been identified and characterized However, fish ISGs represent an exciting, largely unexplored avenue of antiviral effector research and present an opportunity to assess how IFN systems have been shaped by whole genome duplication events. This review summarizes advances in identification of bona fide teleost ISGs and examines studies in elucidating the antiviral mechanisms of con-served ISGs, including IFIT1, Mx, Nmi and IFP35, Viperin, TRIMs, and ISG15. Teleost-specific gene expansions and isoform divergence, particularly in the development of the fish novel TRIM family, will be considered under each relevant ISG. Under-standing teleost ISG biology promises not only to improve antiviral strategies in aquaculture but also to reveal novel antiviral principles with translational relevance for human health.