Genome editing of FTR42 improves zebrafish survival against virus infection by enhancing IFN immunity
Zi-Ling Qu, Xiu-Ying Gong, Lili An, Hao-Yu Sun, Wen‐Hao Guo, Hong-Yu Luan, Mengyao Wu, Cheng Dan, Jian‐Fang Gui, Yi-Bing Zhang
Abstract
The development of CRISPR-Cas9 technology introduces an efficient tool for precise engineering of fish genomes. With a short reproduction cycle, zebrafish infection mode can be referenced as antiviral breeding researches in aquaculture fish. Previously we identified a crucian carp-specific gene ftrca1 as an inhibitor of interferon response in vitro . Here, we demonstrate that genome editing of zebrafish ftr42, a homolog of ftrca1 , generates a zebrafish mutant ( ftr42 lof/lof ) with an improved resistance to SVCV infection. Zebrafish ftr42 acts as a virus-induced E3 ligase and downregulates IFN antiviral response by facilitating TBK1 protein degradation and also IRF7 mRNA decay. Genome editing results in loss of function of zebrafish ftr42 , which enables zebrafish to have enhanced interferon response, thus improving zebrafish survival against virus infection. Our results suggest that fine-tuning fish IFN innate immunity through genome editing of negative regulators can genetically improve viral resistance in fish.