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学科主题基础医学
Apolipoprotein E Mediates Attachment of Clinical Hepatitis C Virus to Hepatocytes by Binding to Cell Surface Heparan Sulfate Proteoglycan Receptors
Jiang, Jieyun1; Wu, Xianfang2; Tang, Hengli2; Luo, Guangxiang1,3,4
刊名PLOS ONE
2013-07-02
DOI10.1371/journal.pone.0067982
8期:7
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
资助者National Institutes of Health ; NSFC ; National Institutes of Health ; NSFC
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]NONSTRUCTURAL PROTEIN 5A ; TARGET-CELLS ; INFECTION ; GLYCOSAMINOGLYCANS ; PARTICLES ; CULTURE ; GLYCOPROTEIN ; INTERACTS ; INHIBIT ; DOMAIN
英文摘要

Our previous studies demonstrated that the cell culture-grown hepatitis C virus of genotype 2a (HCVcc) uses apolipoprotein E (apoE) to mediate its attachment to the surface of human hepatoma Huh-7.5 cells. ApoE mediates HCV attachment by binding to the cell surface heparan sulfate (HS) which is covalently attached to the core proteins of proteoglycans (HSPGs). In the present study, we further determined the physiological importance of apoE and HSPGs in the HCV attachment using a clinical HCV of genotype 1b (HCV1b) obtained from hepatitis C patients and human embryonic stem cell-differentiated hepatocyte-like cells (DHHs). DHHs were found to resemble primary human hepatocytes. Similar to HCVcc, HCV1b was found to attach to the surface of DHHs by the apoE-mediated binding to the cell surface HSPGs. The apoE-specific monoclonal antibody, purified HSPGs, and heparin were all able to efficiently block HCV1b attachment to DHHs. Similarly, the removal of heparan sulfate from cell surface by treatment with heparinase suppressed HCV1b attachment to DHHs. More significantly, HCV1b attachment was potently inhibited by a synthetic peptide derived from the apoE receptor-binding region as well as by an HSPG-binding peptide. Likewise, the HSPG-binding peptide prevented apoE from binding to heparin in a dose-dependent manner, as determined by an in vitro heparin pull-down assay. Collectively, these findings demonstrate that HSPGs serve as major HCV attachment receptors on the surface of human hepatocytes to which the apoE protein ligand on the HCV envelope binds.

语种英语
所属项目编号AI097318 ; AI091953 ; 81130082
资助者National Institutes of Health ; NSFC ; National Institutes of Health ; NSFC
WOS记录号WOS:000321341000125
引用统计
被引频次:25[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/400002259/57622
专题基础医学院_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.Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA
3.Univ Alabama Birmingham, Sch Med, Dept Microbiol, Birmingham, AL 35294 USA
4.Peking Univ, Coll Basic Med Sci, Dept Microbiol, Beijing 100871, Peoples R China
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GB/T 7714
Jiang, Jieyun,Wu, Xianfang,Tang, Hengli,et al. Apolipoprotein E Mediates Attachment of Clinical Hepatitis C Virus to Hepatocytes by Binding to Cell Surface Heparan Sulfate Proteoglycan Receptors[J]. PLOS ONE,2013,8(7).
APA Jiang, Jieyun,Wu, Xianfang,Tang, Hengli,&Luo, Guangxiang.(2013).Apolipoprotein E Mediates Attachment of Clinical Hepatitis C Virus to Hepatocytes by Binding to Cell Surface Heparan Sulfate Proteoglycan Receptors.PLOS ONE,8(7).
MLA Jiang, Jieyun,et al."Apolipoprotein E Mediates Attachment of Clinical Hepatitis C Virus to Hepatocytes by Binding to Cell Surface Heparan Sulfate Proteoglycan Receptors".PLOS ONE 8.7(2013).
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