机构：[1]Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong, PR China.[2]The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510120, PR China.广东省中医院[3]Guangdong Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, Guangdong, PR China.[4]First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong, PR China.深圳市中医院深圳医学信息中心
Zika virus (ZIKV) is a re-emerging RNA virus and causes major public health events due to its link to severe neurological complications in foetuses and neonates. The cGAS-STING signalling pathway regulates innate immunity and plays an important role in the invasion of DNA and RNA viruses. This study reveals a distinct mechanism by which ZIKV restricts the cGAS-STING signalling to repress IFN-β expression. ZIKV attenuates IFN-β expression induced by DNA viruses (herpes simplex virus type 1, HSV-1) or two double-stranded DNAs (dsDNA90 and HSV120) in mouse embryonic fibroblasts (MEFs). Notably, ZIKV NS5, the viral RNA-dependent RNA polymerase, was responsible for the repression of IFN-β. NS5 interacts with STING in the cytoplasm, suppresses IRF3 phosphorylation and nucleus localization and promotes the cleavage of STING K48-linked polyubiquitination. Furthermore, the NS5 methyltransferase (MTase) domain interacts with STING to restrict STING-induced IFN-β expression. Interestingly, point mutation analyses of conserved methyltransferase active site residue D146 indicate that it is critical for repressing IFN-β expression induced by STING stimulation in cGAS-STING signalling.
基金：
This research was funded by Science and Technology Planning Project of Guangzhou, grant number no. 201804010029, the National Nature ScienceFoundation of China, grant nos 81803813, 81973549, the Science and Technology Planning Project of Guangdong Province Office of Education, grantnumber 2014GKXM032, and GZUCM First-class Universities and Top Disciplines Projects, grant nos 2019KYTD102 and A1-AFD018191A17
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类|4 区医学
小类|3 区生物工程与应用微生物4 区病毒学
最新[2025]版：
大类|4 区医学
小类|3 区生物工程与应用微生物4 区病毒学
第一作者：
第一作者机构：[1]Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong, PR China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Li Yuting,Li Zhaoxin,Zou Haimei,et al.A conserved methyltransferase active site residue of Zika virus NS5 is required for the restriction of STING activation and interferon expression[J].The Journal Of General Virology.2024,105(2):doi:10.1099/jgv.0.001954.
APA：
Li Yuting,Li Zhaoxin,Zou Haimei,Zhou Peiwen,Huo Yuhang...&Wang Xiao.(2024).A conserved methyltransferase active site residue of Zika virus NS5 is required for the restriction of STING activation and interferon expression.The Journal Of General Virology,105,(2)
MLA：
Li Yuting,et al."A conserved methyltransferase active site residue of Zika virus NS5 is required for the restriction of STING activation and interferon expression".The Journal Of General Virology 105..2(2024)
