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学科主题: 基础医学
题名:
Syndecan-1 Serves as the Major Receptor for Attachment of Hepatitis C Virus to the Surfaces of Hepatocytes
作者: Shi, Qing1,2; Jiang, Jieyun1; Luo, Guangxiang1,2,3
刊名: JOURNAL OF VIROLOGY
发表日期: 2013-06-01
DOI: 10.1128/JVI.03475-12
卷: 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
所属项目编号: AI091953 ; AI097318 ; 81130082
项目资助者: NIH/NIAID ; NSFC
WOS记录号: WOS:000319508600031
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52492
Appears in Collections:基础医学院_病原生物学系_期刊论文

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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

Recommended Citation:
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.
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