Fish virus-induced interferon exerts antiviral function through Stat1 pathway.

Virus-induced interferons (IFNs) have been identified in various fish species and display antiviral activities similar to mammalian type I IFNs. However, apart from the mammalian IFN system, the IFN signaling pathway remains largely unknown. Using transient transfection and recombinant protein, we are reporting in this study that a crucian carp (Carassius auratus L.) IFN exhibits strong antiviral activity against grass carp hemorrhagic virus (GCHV) infection and also mediates Poly I:C-induced antiviral response, which correlates with its ability to induce a set of IFN-stimulated genes (ISGs). Strikingly, overexpression of wild-type Stat1 increases the effects of IFN on both the expression of ISGs and the inhibition of virus infection, whereas a dominant negative mutant of Stat1 (Stat1-Delta C), which lacks of the C-terminal transcriptional activation domain (TAD), inhibits the antiviral activity of IFN and reduces the expression of ISGs, demonstrating that fish IFN induces the expression of ISGs and host antiviral response through Stat1 pathway reminiscent that of mammalian IFNs. Significantly, unlike mammalian type I IFNs, recombinant fish IFN is able to upregulate IFN itself, which is enhanced by overexpression of Stat1 but impaired by knockdown of Stat1, indicating a positive feedback loop in regulation of IFN itself. These results provide strong evidence for the existence of an evolutionary conserved Stat1 pathway between fish and mammals, which is indispensable for fish virus-induced IFN antiviral response.

Yu FF ，Zhang YB ，Liu TK ，Liu Y ，Sun F ，Jiang J ，Gui JF ... -  《-》

The innate immune response to grass carp hemorrhagic virus (GCHV) in cultured Carassius auratus blastulae (CAB) cells.

Zhang YB ，Jiang J ，Chen YD ，Zhu R ，Shi Y ，Zhang QY ，Gui JF ... -  《DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY》

Gig1, a novel antiviral effector involved in fish interferon response.

Vertebrate interferon (IFN) response defenses against viral infection through the induction of hundreds of IFN-stimulated genes (ISGs). Most ISGs are conserved across vertebrates; however, little is known about the species-specific ISGs. In this study, we reported that grass carp reovirus (GCRV)-induced gene 1 (Gig1), previously screened as a virus-induced gene from UV-inactivated GCRV-infected crucian carp (Carassius auratus) blastulae embryonic (CAB) cells, was a typical fish ISG, which was significantly induced by intracellular poly(I:C) through retinoic acid-inducible gene I (RIG-I)-like receptors-triggered IFN signaling pathway. Transient or stable overexpression of Gig1 prevented GCRV replication efficiently in cultured fish cells. Strikingly, Gig1 homologs were found exclusively in fish species forming a novel gene family. These results illustrate that there exists a Gig1 gene family unique to fish species and the founding gene mediates a novel fish IFN antiviral pathway.

Sun F ，Zhang YB ，Jiang J ，Wang B ，Chen C ，Zhang J ，Gui JF ... -  《-》

Characterization of fish IRF3 as an IFN-inducible protein reveals evolving regulation of IFN response in vertebrates.

Sun F ，Zhang YB ，Liu TK ，Gan L ，Yu FF ，Liu Y ，Gui JF ... -  《-》

Identification of two novel interferon-stimulated genes from cultured CAB cells induced by UV-inactivated grass carp hemorrhage virus.

Zhang YB ，Gui JF 《DISEASES OF AQUATIC ORGANISMS》