LGP2 is essential for zebrafish survival through dual regulation of IFN antiviral response
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-functi...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222010938 |
| _version_ | 1798041128904163328 |
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| author | Xiu-Ying Gong Qi-Min Zhang Xiang Zhao Yi-Lin Li Zi-Ling Qu Zhi Li Cheng Dan Jian-Fang Gui Yi-Bing Zhang |
| author_facet | Xiu-Ying Gong Qi-Min Zhang Xiang Zhao Yi-Lin Li Zi-Ling Qu Zhi Li Cheng Dan Jian-Fang Gui Yi-Bing Zhang |
| author_sort | Xiu-Ying Gong |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T22:17:10Z |
| format | Article |
| id | doaj.art-5aad2e18442a4640b9b564f0c2f5ec0d |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-11T22:17:10Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-5aad2e18442a4640b9b564f0c2f5ec0d2022-12-22T04:00:21ZengElsevieriScience2589-00422022-08-01258104821LGP2 is essential for zebrafish survival through dual regulation of IFN antiviral responseXiu-Ying Gong0Qi-Min Zhang1Xiang Zhao2Yi-Lin Li3Zi-Ling Qu4Zhi Li5Cheng Dan6Jian-Fang Gui7Yi-Bing Zhang8State 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, ChinaState 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, ChinaState 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, ChinaState 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, ChinaState 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, ChinaState Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaState 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, ChinaState 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, ChinaState 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004222010938BiochemistryImmunologyVirology |
| spellingShingle | Xiu-Ying Gong Qi-Min Zhang Xiang Zhao Yi-Lin Li Zi-Ling Qu Zhi Li Cheng Dan Jian-Fang Gui Yi-Bing Zhang LGP2 is essential for zebrafish survival through dual regulation of IFN antiviral response iScience Biochemistry Immunology Virology |
| title | LGP2 is essential for zebrafish survival through dual regulation of IFN antiviral response |
| title_full | LGP2 is essential for zebrafish survival through dual regulation of IFN antiviral response |
| title_fullStr | LGP2 is essential for zebrafish survival through dual regulation of IFN antiviral response |
| title_full_unstemmed | LGP2 is essential for zebrafish survival through dual regulation of IFN antiviral response |
| title_short | LGP2 is essential for zebrafish survival through dual regulation of IFN antiviral response |
| title_sort | lgp2 is essential for zebrafish survival through dual regulation of ifn antiviral response |
| topic | Biochemistry Immunology Virology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222010938 |
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