Fish viperin exerts a conserved antiviral function through RLR-triggered IFN signaling pathway

• Crucian carp viperin is induced at mRNA and protein levels by fish IFNs, IFN stimuli and signaling molecules.
• Crucian carp viperin promoter is activated by two types of fish IFNs, IFN stimuli and all kinds of signaling molecules.
• Intracellular poly(I:C) upregulates crucian carp viperin through RLR-triggered IFN signaling pathway.
• Crucian carp viperin is able to inhibit GCRV replication in cultured fish cells.

Mammalian viperin is a typical interferon (IFN)-induced antiviral protein. Fish have viperin homologs; however, little is known about the expression regulation of fish viperins. In this study, we report the expression regulation and antiviral function of a fish viperin from crucian carp Carassius auratus during IFN response. Crucian carp viperin is induced at mRNA and protein levels by fish IFNs and IFN stimuli such as poly(I:C). Consistently, this gene promoter contains multiple transcription factor binding sites including IFN-stimulated response elements (ISRE) and IFN gamma activation sequences (GAS), and is activated by two types of fish IFNs and also by the intracellular and extracellular poly(I:C). Activation of crucian carp viperin promoter by the intracellular poly(I:C) is mediated by retinoic acid-inducing gene I (RIG-I)-like receptors (RLR)-triggered IFN signaling pathway, which is further verified by the findings that each signaling molecule of RLR pathway is able to induce the expression of crucian carp viperin at mRNA and protein levels. Finally, overexpression of crucian carp viperin in cultured fish cells confers significant protection against infection of grass carp reovirus (GCRV). These data suggest that similar to mammalian homologs, crucian carp viperin exerts a conserved function through RLR-triggered IFN signaling pathway.