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学科主题基础医学
Syndecan-1 Serves as the Major Receptor for Attachment of Hepatitis C Virus to the Surfaces of Hepatocytes
Shi, Qing1,2; Jiang, Jieyun1; Luo, Guangxiang1,2,3
刊名JOURNAL OF VIROLOGY
2013-06-01
DOI10.1128/JVI.03475-12
87期:12页:6866-6875
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Virology
研究领域[WOS]Virology
关键词[WOS]HERPES-SIMPLEX-VIRUS ; HEPARAN-SULFATE PROTEOGLYCANS ; DENSITY-LIPOPROTEIN RECEPTOR ; NONSTRUCTURAL PROTEIN 5A ; HUMAN APOLIPOPROTEIN-E ; B TYPE-I ; DC-SIGN ; CELL-CULTURE ; HEPARIN/HEPARAN SULFATE ; INITIAL INTERACTION
英文摘要

Our recent studies demonstrated that apolipoprotein E mediates cell attachment of hepatitis C virus (HCV) through interactions with the cell surface heparan sulfate (HS). HS is known to covalently attach to core proteins to form heparan sulfate proteoglycans (HSPGs) on the cell surface. The HSPG core proteins include the membrane-spanning syndecans (SDCs), the lycosylphosphatidylinositol-linked glypicans (GPCs), the basement membrane proteoglycan perlecan (HSPG2), and agrin. In the present study, we have profiled each of the HSPG core proteins in HCV attachment. Substantial evidence derived from our studies demonstrates that SDC1 is the major receptor protein for HCV attachment. The knockdown of SDC1 expression by small interfering RNA (siRNA)-induced gene silence resulted in a significant reduction of HCV attachment to Huh-7.5 cells and stem cell-differentiated human hepatocytes. The silence of SDC2 expression also caused a modest decrease of HCV attachment. In contrast, the siRNA-mediated knockdown of other SDCs, GPCs, HSPG2, and agrin had no effect on HCV attachment. More importantly, ectopic expression of SDC1 was able to completely restore HCV attachment to Huh-7.5 cells in which the endogenous SDC1 expression was silenced by specific siRNAs. Interestingly, mouse SDC1 is also fully functional in mediating HCV attachment when expressed in the SDC1-deficient cells, consistent with recent reports that mouse hepatocytes are also susceptible to HCV infection when expressing other key HCV receptors. Collectively, our findings demonstrate that SDC1 serves as the major receptor protein for HCV attachment to cells, providing another potential target for discovery and development of antiviral drugs against HCV.

语种英语
WOS记录号WOS:000319508600031
项目编号AI091953 ; AI097318 ; 81130082
资助机构NIH/NIAID ; NSFC
引用统计
被引频次:52[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52492
专题北京大学基础医学院_病原生物学系
作者单位1.Univ Kentucky, Coll Med, Dept Microbiol Immunol & Mol Genet, Lexington, KY 40536 USA
2.Peking Univ, Hlth Sci Ctr, Dept Microbiol, Beijing 100871, Peoples R China
3.Univ Alabama Birmingham, Dept Microbiol, Med Sch Birmingham, Birmingham, AL 35294 USA
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GB/T 7714
Shi, Qing,Jiang, Jieyun,Luo, Guangxiang. Syndecan-1 Serves as the Major Receptor for Attachment of Hepatitis C Virus to the Surfaces of Hepatocytes[J]. JOURNAL OF VIROLOGY,2013,87(12):6866-6875.
APA Shi, Qing,Jiang, Jieyun,&Luo, Guangxiang.(2013).Syndecan-1 Serves as the Major Receptor for Attachment of Hepatitis C Virus to the Surfaces of Hepatocytes.JOURNAL OF VIROLOGY,87(12),6866-6875.
MLA Shi, Qing,et al."Syndecan-1 Serves as the Major Receptor for Attachment of Hepatitis C Virus to the Surfaces of Hepatocytes".JOURNAL OF VIROLOGY 87.12(2013):6866-6875.
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