PUBLICATION
LGP2 is essential for zebrafish survival through dual regulation of IFN antiviral response
- Authors
- Gong, X.Y., Zhang, Q.M., Zhao, X., Li, Y.L., Qu, Z.L., Li, Z., Dan, C., Gui, J.F., Zhang, Y.B.
- ID
- ZDB-PUB-220820-6
- Date
- 2022
- Source
- iScience 25: 104821 (Journal)
- Registered Authors
- Gui, Jian-Fang, Li, Zhi, Zhang, Yi-Bing
- Keywords
- Biochemistry, Immunology, Virology
- MeSH Terms
- none
- PubMed
- 35982787 Full text @ iScience
Citation
Gong, X.Y., Zhang, Q.M., Zhao, X., Li, Y.L., Qu, Z.L., Li, Z., Dan, C., Gui, J.F., Zhang, Y.B. (2022) LGP2 is essential for zebrafish survival through dual regulation of IFN antiviral response. iScience. 25:104821.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping