Interferon (IFN) system in fish: research progress and contributions from China

Interferons (IFNs) are a class of cytokines with pleiotropic immunological and biological functions, such as antiviral, antibacterial and immunomodulatory functions. In vertebrates, IFNs play pivotal roles in innate immune system, and can also coordinate effective adaptive immunity. Up to now, four types of IFNs, i.e., type I, type II, type III and type IV IFNs, have been reported in vertebrates. As a diversified lineage of vertebrates, fish represents the earliest group of vertebrates to possess well-defined and complicated IFN systems, and they are considered as important for the study of composition, function, and evolution of IFN systems. According to phylogenetic relationships, fish type I IFNs are classified into eight subgroups, namely IFNa − IFNf, IFNh and IFNi, which selectively use different receptor complexes to induce the production of interferon stimulated genes (ISGs) through the conserved JAK/STAT signaling pathway, thereby exerting their biological functions, such as antiviral and antibacterial activities. Two members of type II IFNs, IFN-γ and IFN-γrel exist in fish, and they can use CRFB13/CRFB6 and CRFB17 to transfer signaling through STAT1, respectively. Type III IFNs and their receptor subunits have been identified in cartilaginous fish, although not in teleost fish. Type IV IFN is a new IFN identified recently in fish and primitive mammals, which has a significant antiviral function with receptors consisting of CRFB12 and CRFB4. In this report, the current achievements of type I, type II, type III and type IV IFNs in fish were reviewed in respect to gene structure, classification and nomenclature, receptor composition and usage, signaling pathway, and immunological function. Contributions from Chinese scientists on fish IFN composition and nomenclature, receptor usage and signaling, crystal structure, functional specialty, and new IFN finding were summarized. The possible future direction was also proposed in relation with the research on fish IFN systems in this article. It is expected that this article will contribute to systematic understanding of fish IFN system, and may also provide information for potential application of IFNs in antiviral and antibacterial practice in aquaculture.