The Peculiar Characteristics of Fish Type I Interferons

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.

Keywords: evolution; fish innate immunity; type I IFN.

Figure 1

Schematic phylogenetic tree of fishes. Taxonomy from [20]. The thick black arrow indicates a whole genome duplication (WGD) during the early evolution of ray-finned fishes. X indicate examples of posterior WGD in specific branches. Genome sequence is available for all species indicated with *. Species in bold letters are mentioned in Table 1.

Figure 2

Receptors of virus induced IFN in zebrafish and human. Adapted from [21]. Intracellular regions are represented by round boxes, and D200 domains by rectangular boxes. IFN binding to each receptor are represented on the right.

Figure 3

Different mechanisms lead to transcripts encoding secreted and non secreted IFN (group I). Exons (numbered 1–3) are represented as boxes. In transcripts, spliced introns are represented by dotted lines, while plain lines correspond to un-spliced introns. ATG corresponding to the secreted IFN open reading frame (ORF) are indicated by a black arrow. * denote alternative transcription start points in zebrafish. Note that mechanisms leading to production of mRNA encoding secreted IFN are different in zebrafish and rainbow trout (alternative transcription start versus alternative splicing). Adapted from [27,30,31].

Figure 4

Evolution of the type I IFN locus. (A) Current structure of scn4a/ahrgap27 loci in various vertebrate genomes, illustrating the loss of type I IFN gene in this region likely from the common ancestor of amniotes. The color code for the different markers of this synteny group is represented on the right of the panel. IFNs of the four- and two-cysteine types are noted as 4C and 2C; (B) Tentative reconstitution of the evolution of this region in Vertebrates, illustrating the presence of type I IFN genes in the scn4a/ahrgap27 locus from the common ancestors of fish and tetrapods, and their loss during the evolution of Amniotes.