In the previous studies conducted by the Research Group of Fish Developmental Genetics and Cell Engineering (Principal Investigator: Prof. Gui Jianfang) at Institute of Hydrobiology, Chinese Academy of Sciences (IHB), the conserved IFN-STAT1 signaling cascade had been demonstrated to exist in fish (Mol Immunol. 47:2330-2341). Distinct from mammalian IRF3, fish IRF3 had evolved an unique mechanism to regulate IFN response against virua infection (J Immunol, 185:7573-7582). Recently, researchers from Prof. Gui’s research group have confirmed the RLR-mediated IFN activation is conserved from fish to mammals. The characterization and functional analysis of several pivotal signaling molecules of RLR pathway, including RIG-I, MDA5, MITA, TBK1 and IRF3, have demonstrated that the cytosolic sensors RIG-I/MDA5 activate the IFN response against viral infection via MITA-TBK1-IRF3 pathway. Further experiments indicate that LGP2, the third member of RLR family, functions as a negative regulator of RIG-I/MDA5-mediated IFN activation.  

Zebrafish genome contains four virus-induced IFN genes that are divided into two groups: group I IFNs (IFN1 and IFN4), and group II IFNs (IFN2 and IFN3). Further characterization of distinct IFN gene activation reveals that zebrafish IFN1 and IFN3 are induced by the conserved RLR signaling cascade but are dependent on distinct transcription factors. Whereas fish IFN genes cannot be classified into IFNa or IFNb, zebrafish IFN1 is primarily regulated by IRF3, thereby resembling that of IFNb, and zebrafish IFN3 is regulated by IRF7, thereby resembling of those of IFNas. In contrast with mammalian IFNa/b, zebrafish IFN1 and IFN3 are induced by the basally expressed IRF3 or IRF7, both of which are upregulated by IFN and virus infection. Collectively, these data suggest that IFN genes in fish and mammals have evolved independently to acquire a similar mechanism triggering their expression. 

This work was supported by grants from the 973 National Basic Research Program of China.The research was fulfilled by IHB Ph. D student Sun Fan et al. under the supervision of Profs. Zhang Yibing and Gui Jianfang. The related article was published online in Journal of Immunology. (http://www.jimmunol.org/content/early/2011/07/27/jimmunol.1100642.abstract).