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学科主题: 基础医学
题名:
Hepatitis C Virus Attachment Mediated by Apolipoprotein E Binding to Cell Surface Heparan Sulfate
作者: Jiang, Jieyun1; Cun, Wei1; Wu, Xianfang2; Shi, Qing1,3; Tang, Hengli2; Luo, Guangxiang1,3
刊名: JOURNAL OF VIROLOGY
发表日期: 2012-07-01
DOI: 10.1128/JVI.07222-11
卷: 86, 期:13, 页:7256-7267
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]: DENSITY-LIPOPROTEIN RECEPTOR ; PRIMARY HUMAN HEPATOCYTES ; NONSTRUCTURAL PROTEIN 5A ; B TYPE-I ; SCAVENGER RECEPTOR ; E ISOFORMS ; PEGINTERFERON ALPHA-2A ; TRANSPORT PROTEIN ; INFECTIOUS VIRUS ; VIRAL-HEPATITIS
英文摘要:

Viruses are known to use virally encoded envelope proteins for cell attachment, which is the very first step of virus infection. In the present study, we have obtained substantial evidence demonstrating that hepatitis C virus (HCV) uses the cellular protein apolipoprotein E (apoE) for its attachment to cells. An apoE-specific monoclonal antibody was able to efficiently block HCV attachment to the hepatoma cell line Huh-7.5 as well as primary human hepatocytes. After HCV bound to cells, however, anti-apoE antibody was unable to inhibit virus infection. Conversely, the HCV E2-specific monoclonal antibody CBH5 did not affect HCV attachment but potently inhibited HCV entry. Similarly, small interfering RNA-mediated knockdown of the key HCV receptor/coreceptor molecules CD81, claudin-1, low-density lipoprotein receptor (LDLr), occludin, and SR-BI did not affect HCV attachment but efficiently suppressed HCV infection, suggesting their important roles in HCV infection at postattachment steps. Strikingly, removal of heparan sulfate from the cell surface by treatment with heparinase blocked HCV attachment. Likewise, substitutions of the positively charged amino acids with neutral or negatively charged residues in the receptor-binding region of apoE resulted in a reduction of apoE-mediating HCV infection. More importantly, mutations of the arginine and lysine to alanine or glutamic acid in the receptor-binding region ablated the heparin-binding activity of apoE, as determined by an in vitro heparin pulldown assay. HCV attachment could also be inhibited by a synthetic peptide derived from the apoE receptor-binding region. Collectively, these findings demonstrate that apoE mediates HCV attachment through specific interactions with cell surface heparan sulfate.

语种: 英语
所属项目编号: AI091953 ; AI097318 ; AI092074 ; KSEF-148-502-10-272 ; AI079150
项目资助者: NIH ; Kentucky Science and Engineering Foundation
WOS记录号: WOS:000305501600024
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54796
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 40506 USA
2.Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA
3.Peking Univ, Hlth Sci Ctr, Dept Microbiol, Beijing 100871, Peoples R China

Recommended Citation:
Jiang, Jieyun,Cun, Wei,Wu, Xianfang,et al. Hepatitis C Virus Attachment Mediated by Apolipoprotein E Binding to Cell Surface Heparan Sulfate[J]. JOURNAL OF VIROLOGY,2012,86(13):7256-7267.
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