Experimental study reveals distinct transcriptional regulation and receptor signaling of type IV interferon in Carassius gibelio, highlighting an evolutionarily divergent antiviral cytokine lineage.
It was recently shown that vertebrates, ranging from fish to primitive mammals, possess type IV IFN (IFNυ). However, their precise function and elaborate signaling remains unknown. In this study, CaIFNυ was identified from Carassius gibelio and its transcriptional regulation and signaling was further investigated. Firstly, CaIFNυ displays significant differences in the distribution, magnitude, and kinetics of its antiviral properties compared with CaIFNa1, a typical type I IFN from C. gibelio. Secondly, IRF1/3/7 differentially activated CaIFNυ through homo- or heteroprotein complexes in a dose-dependent fashion and NF-κB (p65) was the most effective stimulator. Thirdly, CaIFNυ initiates the antiviral ISGs through the JAK-STAT as well as MAPK and PI3K signaling pathways by binding to the extra-cellular region of CaCRFB4 and CaCRFB12. Taken together, these findings reveal that CaIFNυ belonges to an antiviral cytokine lineage which is distinct from CaIFNa1.
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Dai et al. (2025) studied this question.
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