Abstract
Antiviral type I interferons (IFNs) have been discovered in fish. Genomic studies revealed their considerable number in many species; some genes encode secreted and non-secreted isoforms. Based on cysteine motifs, fish type I IFNs fall in two subgroups, which use two different receptors. Mammalian type I IFN genes are intronless while type III have introns; in fish, all have introns, but structurally, both subgroups belong to type I. Type I IFNs likely appeared early in vertebrates as intron containing genes, and evolved in parallel in tetrapods and fishes. The diversity of their repertoires in fish and mammals is likely a convergent feature, selected as a response to the variety of viral strategies. Several alternative nomenclatures have been established for different taxonomic fish groups, calling for a unified system. The specific functions of each type I gene remains poorly understood, as well as their interactions in antiviral responses. However, distinct induction pathways, kinetics of response, and tissue specificity indicate that fish type I likely are highly specialized, especially in groups where they are numerous such as salmonids or cyprinids. Unravelling their functional integration constitutes the next challenge to understand how these cytokines evolved to orchestrate antiviral innate immunity in vertebrates.
Highlights
Interferons (IFNs) are the hallmark of vertebrate innate immunity to viruses
Gene identification in expressed sequence tag (EST) and genomic libraries opened the way to the characterization of the fish IFN system, including IFN receptors, key factors of the signalling pathways leading to IFN and ISG induction, and ISG repertoires
Since IFN genes with 4C appear ancestral, the most parsimonious hypothesis would be that the original 4C gene had with 4C appear ancestral, the most parsimonious hypothesis would be that the original 4C gene a tandem duplication, giving rise to a 2C neighbour, prior to the teleost whole genome duplication (WGD), endowing early teleosts with (2C 4C) and (2C 4C) loci, which would have further evolved in the diversity of type I IFN
Summary
Interferons (IFNs) are the hallmark of vertebrate innate immunity to viruses. IFNs belong to the class II helical cytokine family, and can be classified into three families (type I IFNs, which include IFNα and -β, type II or γ IFN, and type III or λ IFNs) based on their structural and functional properties, and on their receptors. Gene identification in expressed sequence tag (EST) and genomic libraries opened the way to the characterization of the fish IFN system, including IFN receptors, key factors of the signalling pathways leading to IFN and ISG induction, and ISG repertoires. These studies revealed an astonishing diversity of fish type I IFNs and their complex regulation in these organisms. We review here this “alternative” fish IFN system, which evolved in parallel to the one known in tetrapods
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