Ctenopharyngodon idella (grass carp) pVHL suppresses antiviral innate immunity by targeting MAVS for degradation upon GCRV infection

Abstract

Grass carp reovirus (GCRV), a double-stranded RNA virus, has been identified as the causative pathogen of grass carp hemorrhagic disease (GCHD), which is one of the most severe diseases in freshwater aquaculture in China. Previously, we reported that the von Hippel–Lindau protein (pVHL) suppresses antiviral innate immunity during RNA virus infection by targeting the mitochondrial antiviral signaling (MAVS) protein for degradation. However, the role of pVHL in the innate immunity against GCRV is still not clear. In the present study, the VHL gene of grass carp was cloned, and the VHL gene was found to be conserved throughout the species. Using zebrafish as a model, we showed that disruption of vhl facilitates antiviral gene expression during GCRV infection. After GCRV infection or poly I:C stimulation, the mRNA level of Ci-VHL was significantly increased. Furthermore, Ci-pVHL interacts with Ci-MAVS, promotes degradation of Ci-MAVS, and inhibits Ci-MAVS-mediated interferon (IFN) activation. In addition, we screened 249 grass carp samples and identified three different types of single nucleotide polymorphisms (SNPs) within the Ci-VHL gene. The effect of each SNP on antiviral gene expression and virus replication following GCRV infection was also investigated. To conclude, the findings presented here may provide valuable insights regarding the function of pVHL in innate immunity against GCRV. Furthermore, VHL may serve as a promising target for the breeding of anti-GCRV grass carp strains.