Genome editing of FTR42 improves zebrafish survival against virus infection by enhancing IFN immunity

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 ftrc...

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Published in:iScience 2024-04, Vol.27 (4), p.109497-109497, Article 109497
Main Authors: 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
Format: Article
Language:English
Subjects:
Biological sciences
Gene process
Molecular biology
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Summary: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 (ftr42lof/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. [Display omitted] •FTR42 loss-of-function zebrafish show improved resistance to virus infection•Zebrafish FTR42 facilitates TBK1 protein degradation to inhibit IFN response•Zebrafish FTR42 facilitates IRF7 mRNA decay to inhibit IFN response Biological sciences; Gene process; Molecular biology
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2024.109497