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

Zi-Ling Qu; Xiu-Ying Gong; Li-Li An; Hao-Yu Sun; Wen-Hao Guo; Hong-Yu Luan; Meng-Yao Wu; Cheng Dan; Jian-Fang Gui; Yi-Bing Zhang

doi:10.1016/j.isci.2024.109497

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

iScience. 2024 Mar 12;27(4):109497. doi: 10.1016/j.isci.2024.109497. eCollection 2024 Apr 19.

Authors

Zi-Ling Qu^{1

2}, Xiu-Ying Gong^{1

2}, Li-Li An^{1

2}, Hao-Yu Sun^{1

2}, Wen-Hao Guo^{1

2}, Hong-Yu Luan¹, Meng-Yao Wu^{1

2}, Cheng Dan^{1

2}, Jian-Fang Gui^{1

2

3}, Yi-Bing Zhang^{1

2

3}

Affiliations

¹ Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
² University of Chinese Academy of Sciences, Beijing 10049, China.
³ The Innovation Academy of Seed Design, Chinese Academy of Sciences, Wuhan 430072, China.

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.

Keywords: Biological sciences; Gene process; Molecular biology.