Ctenopharyngodon idella (grass carp) SIRT7 negatively regulates anti-GCRV innate immunity by promoting IRF3 and IRF7 degradation

Abstract

Ctenopharyngodon idella (grass carp) is widely regarded as one of the world's most economically important freshwater aquaculture species. Notably, grass carp reovirus (GCRV), classified as a double-stranded RNA (dsRNA) virus, has been identified as the causative pathogen of grass carp hemorrhagic disease (GCHD), which has resulted in substantial economic losses. This study aims to identify key genes involved in anti-GCRV innate immunity, with the ultimate goal of breeding anti-GCRV grass carp strains. In the present study, using zebrafish as a model, we demonstrated that sirt7 deficiency enhances antiviral gene expression during GCRV infection. Subsequent cloning and analysis of the grass carp SIRT7 gene revealed its conservation across different species. The Ci-SIRT7 mRNA level was found to be highest in grass carp liver, and following GCRV infection, the Ci-SIRT7 mRNA level in the liver was kept stable. Conversely, the Ci-SIRT7 mRNA level was found to be comparatively low in grass carp intestine, and following GCRV infection, the Ci-SIRT7 mRNA level in the intestine was markedly induced. From a mechanistic perspective, Ci-SIRT7 has been observed to interact with Ci-IRF3 and Ci-IRF7, thereby inhibiting Ci-IRF3/7-mediated IFN activation. Furthermore, the results of this study demonstrated that Ci-SIRT7 promotes the ubiquitination and degradation of Ci-IRF3 and Ci-IRF7. In summary, the results presented here may contribute to the understanding of the role of grass carp SIRT7 in innate immunity against GCRV. In particular, SIRT7 is emerging as a promising target for developing novel grass carp strains resistant to GCRV infection.