中国病毒学2023，Issue(2) ：222-232.

Splicing factor SF3B3,a NS5-binding protein,restricts ZIKV infection by targeting GCH1

Tanxiu Chen Hao Yang Penghui Liu Moliduer Hamiti Xintian Zhang Yi Xu Wenqi Quan Yong Zhang Wenhai Yu Li Jiao Tingfu Du Juemin Xi Bin Yin Wei Zhou Shuaiyao Lu Xiaozhong Peng
中国病毒学2023，Issue(2) ：222-232.
✕
  • NETL
  • NSTL
  • 万方数据

Splicing factor SF3B3,a NS5-binding protein,restricts ZIKV infection by targeting GCH1

Tanxiu Chen 1Hao Yang 2Penghui Liu 2Moliduer Hamiti 3Xintian Zhang 2Yi Xu 2Wenqi Quan 2Yong Zhang 2Wenhai Yu 2Li Jiao 2Tingfu Du 2Juemin Xi 2Bin Yin 3Wei Zhou 4Shuaiyao Lu 2Xiaozhong Peng5
扫码查看

作者信息

  • 1. Institute of Medical Biology,Chinese Academy of Medical Sciences and Peking Union Medical College,Kunming,650031,China;Department of Science and Education,Jiangxi Key Laboratory of Translational Cancer Research,Jiangxi Cancer Hospital,Nanchang 330029,China
  • 2. Institute of Medical Biology,Chinese Academy of Medical Sciences and Peking Union Medical College,Kunming,650031,China
  • 3. The State Key Laboratory of Medical Molecular Biology,Department of Molecular Biology and Biochemistry,Institute of Basic Medical Sciences,Medical Primate Research Center,Neuroscience Center,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100730,China
  • 4. Department of Science and Education,Jiangxi Key Laboratory of Translational Cancer Research,Jiangxi Cancer Hospital,Nanchang 330029,China
  • 5. Institute of Medical Biology,Chinese Academy of Medical Sciences and Peking Union Medical College,Kunming,650031,China;The State Key Laboratory of Medical Molecular Biology,Department of Molecular Biology and Biochemistry,Institute of Basic Medical Sciences,Medical Primate Research Center,Neuroscience Center,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100730,China
  • 折叠

Abstract

Zika virus(ZIKV),a positive-sense single-stranded RNA virus,causes congenital ZIKV syndrome in children and Guillain-Barré Syndrome(GBS)in adults.ZIKV expresses nonstructural protein 5(NS5),a large protein that is essential for viral replication.ZIKV NS5 confers the ability to evade interferon(IFN)signalling;however,the exact mechanism remains unclear.In this study,we employed affinity pull-down and liquid chromatography-tandem mass spectrometry(LC-MS/MS)analyses and found that splicing factor 3b subunit 3(SF3B3)is associated with the NS5-Flag pull-down complex through interaction with NS5.Functional assays showed that SF3B3 over-expression inhibited ZIKV replication by promoting IFN-stimulated gene(ISG)expression whereas silencing of SF3B3 inhibited expression of ISGs to promote ZIKV replication.GTP cyclohydrolase Ⅰ(GCH1)is the first and rate-limiting enzyme in tetrahydrobiopterin(BH4)biosynthesis.NS5 upregulates the expression of GCH1 during ZIKV infection.And GCH1 marginally promoted ZIKV replication via the IFN pathway.Additionally,GCH1 expression is related to the regulation of SF3B3.Overexpression of the SF3B3 protein effectively reduced GCH1 protein levels,whereas SF3B3 knockdown increased its levels.These findings indicated that ZIKV NS5 binding protein SF3B3 contributed to the host immune response against ZIKV replication by modulating the expression of GCH1.

Key words

Nonstructural protein 5(NS5)/Splicing factor 3b subunit 3(SF3B3)/GTP cyclohydrolase Ⅰ(GCH1)/IFN-stimulated gene(ISGs)/IFN signalling Pathway

引用本文复制引用

基金项目

National Key R&D Project of China(2021YFC230170402)

CAMS Innovation Fund for Medical Sciences(2021-1-I2M-038)

出版年

2023
中国病毒学
中国科学院武汉病毒研究所，中国微生物学会

中国病毒学

CSTPCDCSCD北大核心
影响因子：0.393
ISSN：1674-0769
参考文献量49
段落导航相关论文