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.

Contribution of type III interferons to antiviral immunity: location, location, location

“…This is an exciting possibility and would represent a major clinical advance. In addition, type III IFNs have now been shown to play an important role in protecting the lung from fungal infection, 4 suggesting applications beyond the treatment and prophylaxis of viral infection. The potential use of IFN-in the treatment of malignancy is also an area of active research (61).…”

Unique Composition of Intronless and Intron-Containing Type I IFNs in the Tibetan Frog Nanorana parkeri Provides New Evidence To Support Independent Retroposition Hypothesis for Type I IFN Genes in Amphibians

“…In a previous study to explore the possible molecular mechanism in the generation of intronless type I IFNs, a hypothesis was proposed that intronless type I IFN genes in amniotes might have arisen from primitive intron-containing type I IFN genes via a retroposition event when vertebrates migrated from aquatic to terrestrial environments (18). Now, this hypothesis has been generally accepted (19,20), but when this retroposition event might have happened still remains unknown or uninvestigated.…”

Interferon-stimulated genes in zebrafish and human define an ancient arsenal of antiviral immunity

“…Many members of the list appear to have DNA binding capacity and may be classified as transcription factors. * Three IRF (3, 7, 9) and two STAT(1, 2) constitute fundamental components of the type I pathway signaling, and were already present in the LCA of fish and mammals. * BATF2 is a member of the AP-1/ATF family transcription factors that controls the differentiation of immune cells and play key regulatory roles in immune responses. BATF2 promotes TLR7-induced Th1 responses (52).…”

“…* Three IRF (3, 7, 9) and two STAT(1, 2) constitute fundamental components of the type I pathway signaling, and were already present in the LCA of fish and mammals.…”

“…Bony fishes (hereafter simply called “fish”) diverged from the tetrapod lineage about 450My ago, and, since viral infections are a major problem in aquaculture, their IFN system has been the subject of many studies, as reviewed in (6–9). Teleost fish possess several subgroups of type I IFNs (but no type III genes), with strong variation in gene numbers among fish taxa (8). The zebrafish possess four type I IFN genes, named ifnphi1-4 ; only ifnphi1 and ifnphi3 are active at the larval stage (10).…”