LGP2 is essential for zebrafish survival through dual regulation of IFN antiviral response
Xiu-Ying Gong,
Qi-Min Zhang,
Xiang Zhao,
Yi-Lin Li,
Zi-Ling Qu,
Zhi Li,
Cheng Dan,
Jian-Fang Gui,
Yi-Bing Zhang
Affiliations
Xiu-Ying Gong
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 10049, China
Qi-Min Zhang
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 10049, China
Xiang Zhao
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 10049, China
Yi-Lin Li
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 10049, China
Zi-Ling Qu
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 10049, China
Zhi Li
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
Cheng Dan
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 10049, China
Jian-Fang Gui
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 10049, China; The Innovation Academy of Seed Design, Chinese Academy of Sciences, Wuhan 430072, China
Yi-Bing Zhang
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 10049, China; The Innovation Academy of Seed Design, Chinese Academy of Sciences, Wuhan 430072, China; Corresponding author
Summary: In mammals, LGP2 is the enigmatic RLR family member, being initially believed as an inhibitor of RLR-triggered IFN response but subsequently as an activator of MDA5 signaling and an inhibitor of RIG-I signaling. The contradiction happens to fish LGP2. Here, we generate a lgp2 loss-of-function (lgp2lof/lof) zebrafish mutant, which is highly susceptible to SVCV infection, displaying an initially decreased activation of IFN response and a following increased one. Mechanistically, zebrafish LGP2 functions as the essential activator of IFN response dependent on MDA5 at the early stage of viral infection but as a negative regulator by impairing mRNA levels of tbk1 and ikki at the late stage of viral infection. The function switch of LGP2 is related to cellular IFN production during viral infection. Our data demonstrate that zebrafish LGP2 is a key homeostatic regulator of IFN response and thus essential for zebrafish survival against SVCV infection.
