Research
| Title： | Genome editing of FTR42 improves zebrafish survival against virus infection by enhancing IFN immunity |
|---|---|
| First author： | Qu, Zi-Ling; Gong, Xiu-Ying; An, Li-li; Sun, Hao-Yu; Guo, Wen-Hao; Luan, Hong -Yu; Wu, Meng-Yao; Dan, Cheng; Gui, Jian-Fang; Zhang, Yi-Bing |
| Journal： | ISCIENCE |
| Years： | 2024 |
| DOI： | 10.1016/j.isci.2024.109497 |
| 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. |
