Abstract
Interferons (IFNs) are critical soluble factors in the immune system and are composed of three types, (I, II and III) that utilize different receptor complexes IFN-αR1/IFN-αR2, IFN-γR1/IFN-γR2, and IFN-λR1/IL-10R2, respectively. Here we identify IFN-υ from the genomic sequences of vertebrates. The members of class II cytokine receptors, IFN-υR1 and IL-10R2, are identified as the receptor complex of IFN-υ, and are associated with IFN-υ stimulated gene expression and antiviral activity in zebrafish (Danio rerio) and African clawed frog (Xenopus laevis). IFN-υ and IFN-υR1 are separately located at unique and highly conserved loci, being distinct from all other three-type IFNs. IFN-υ and IFN-υR1 are phylogenetically clustered with class II cytokines and class II cytokine receptors, respectively. Therefore, the finding of this IFN ligand-receptor system may be considered as a type IV IFN, in addition to the currently recognized three types of IFNs in vertebrates.
Highlights
The alpha-helical cytokines are divided into two classes, i.e., I and II, based mainly on the utilization of their receptors[1,2], and in mammals, class II cytokines contain interleukins (ILs), including IL-10, IL-19, IL-20, IL-22, IL-24, IL
IFN locus, which is PTPLAD2 - type I IFNs - MTAP gene cluster, is highly conserved from green anole (Anolis carolinensis, a reptile species) to human[7,17,18], but not in tropical clawed frog (Xenopus tropicalis, an amphibian species) which has an intron-containing, five-exon and four-intron type I IFN locus with conserved colinearity when compared to zebrafish (Danio rerio), and has an intronless type I IFN locus without any synteny compared to other vertebrates[17,18]
Type I IFN receptors contain two molecules, CRFB1 and CRFB2, equivalent phylogenetically and functionally to IFNAR2 in mammals, which are known as IFNφ1-R1/IFNAR2-1 and IFNφ2-R1/IFNAR2-2, and are likely derived from gene duplication, and a single CRFB5 known as IFNφ-R2, equivalent to IFNAR110,15,20,23
Summary
The alpha-helical cytokines are divided into two classes, i.e., I and II, based mainly on the utilization of their receptors[1,2], and in mammals, class II cytokines contain interleukins (ILs), including IL-10, IL-19, IL-20, IL-22, IL-24, IL-. IFN locus, which is PTPLAD2 - type I IFNs - MTAP gene cluster, is highly conserved from green anole (Anolis carolinensis, a reptile species) to human[7,17,18], but not in tropical clawed frog (Xenopus tropicalis, an amphibian species) which has an intron-containing, five-exon and four-intron type I IFN locus with conserved colinearity when compared to zebrafish (Danio rerio), and has an intronless type I IFN locus without any synteny compared to other vertebrates[17,18]. Type I IFN receptors contain two molecules, CRFB1 and CRFB2, equivalent phylogenetically and functionally to IFNAR2 in mammals, which are known as IFNφ1-R1/IFNAR2-1 and IFNφ2-R1/IFNAR2-2, and are likely derived from gene duplication, and a single CRFB5 known as IFNφ-R2, equivalent to IFNAR110,15,20,23. The four type I IFNs can be further divided into two groups, group I and group II, with IFN-φ1/φ4 and φ2/φ3, respectively, which signal through the receptor complexes, CRFB1 + CRFB5 and CRFB2 + CRFB5, respectively, to produce antiviral activity[15,20]
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