首页|Splicing factor SF3B3,a NS5-binding protein,restricts ZIKV infection by targeting GCH1
Splicing factor SF3B3,a NS5-binding protein,restricts ZIKV infection by targeting GCH1
扫码查看
点击上方二维码区域，可以放大扫码查看
原文链接
NETL
NSTL
万方数据
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.
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
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
National Key R&D Project of ChinaCAMS Innovation Fund for Medical Sciences
NETL
NSTL
万方数据
