Dai Caijiao, Zhu Yuting, Qian Shiyu, Fan Yihui, Weng Zekun, Li Lijuan, Wang Jianghua, Yuan Junfa
Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China.
National Aquatic Animal Diseases Para-reference laboratory (HZAU), Wuhan, China.
Cell Commun Signal. 2025 Jul 11;23(1):335. doi: 10.1186/s12964-025-02342-5.
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.
最近研究表明，从鱼类到原始哺乳动物的脊椎动物都拥有IV型干扰素（IFNυ）。然而，它们的确切功能和复杂的信号传导仍不清楚。在本研究中，从银鲫中鉴定出CaIFNυ，并进一步研究了其转录调控和信号传导。首先，与银鲫典型的I型干扰素CaIFNa1相比，CaIFNυ在抗病毒特性的分布、强度和动力学方面表现出显著差异。其次，IRF1/3/7通过同型或异型蛋白复合物以剂量依赖性方式差异激活CaIFNυ，而NF-κB（p65）是最有效的刺激因子。第三，CaIFNυ通过与CaCRFB4和CaCRFB12的细胞外区域结合，通过JAK-STAT以及MAPK和PI3K信号通路启动抗病毒ISG。综上所述，这些发现表明CaIFNυ属于一种不同于CaIFNa1的抗病毒细胞因子谱系。
