| pubmed-article:16928753 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16928753 | lifeskim:mentions | umls-concept:C0220847 | lld:lifeskim |
| pubmed-article:16928753 | lifeskim:mentions | umls-concept:C0521026 | lld:lifeskim |
| pubmed-article:16928753 | lifeskim:mentions | umls-concept:C0178539 | lld:lifeskim |
| pubmed-article:16928753 | lifeskim:mentions | umls-concept:C0038720 | lld:lifeskim |
| pubmed-article:16928753 | lifeskim:mentions | umls-concept:C1704675 | lld:lifeskim |
| pubmed-article:16928753 | lifeskim:mentions | umls-concept:C1521761 | lld:lifeskim |
| pubmed-article:16928753 | pubmed:issue | 21 | lld:pubmed |
| pubmed-article:16928753 | pubmed:dateCreated | 2006-10-16 | lld:pubmed |
| pubmed-article:16928753 | pubmed:abstractText | Cellular binding and entry of hepatitis C virus (HCV) are the first steps of viral infection and represent a major target for antiviral antibodies and novel therapeutic strategies. We have recently demonstrated that heparan sulfate (HS) plays a key role in the binding of HCV envelope glycoprotein E2 to target cells (Barth et al., J. Biol. Chem. 278:41003-41012, 2003). In this study, we characterized the HCV-HS interaction and analyzed its inhibition by antiviral host immune responses. Using recombinant envelope glycoproteins, virus-like particles, and HCV pseudoparticles as model systems for the early steps of viral infection, we mapped viral and cellular determinants of HCV-HS interaction. HCV-HS binding required a specific HS structure that included N-sulfo groups and a minimum of 10 to 14 saccharide subunits. HCV envelope binding to HS was mediated by four viral epitopes overlapping the E2 hypervariable region 1 and E2-CD81 binding domains. In functional studies using HCV pseudoparticles, we demonstrate that HCV binding and entry are specifically inhibited by highly sulfated HS. Finally, HCV-HS binding was markedly inhibited by antiviral antibodies derived from HCV-infected individuals. In conclusion, our results demonstrate that binding of the viral envelope to a specific HS configuration represents an important step for the initiation of viral infection and is a target of antiviral host immune responses in vivo. Mapping of viral and cellular determinants of HCV-HS interaction sets the stage for the development of novel HS-based antiviral strategies targeting viral attachment and entry. | lld:pubmed |
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| pubmed-article:16928753 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16928753 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16928753 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:16928753 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:16928753 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16928753 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:16928753 | pubmed:issn | 0022-538X | lld:pubmed |
| pubmed-article:16928753 | pubmed:author | pubmed-author:BlumHubert... | lld:pubmed |
| pubmed-article:16928753 | pubmed:author | pubmed-author:ZhangFumingF | lld:pubmed |
| pubmed-article:16928753 | pubmed:author | pubmed-author:LinhardtRober... | lld:pubmed |
| pubmed-article:16928753 | pubmed:author | pubmed-author:BarthHeidiH | lld:pubmed |
| pubmed-article:16928753 | pubmed:author | pubmed-author:DeplaErikE | lld:pubmed |
| pubmed-article:16928753 | pubmed:author | pubmed-author:BaumertThomas... | lld:pubmed |
| pubmed-article:16928753 | pubmed:author | pubmed-author:BosonBertrand... | lld:pubmed |
| pubmed-article:16928753 | pubmed:author | pubmed-author:PatelArvind... | lld:pubmed |
| pubmed-article:16928753 | pubmed:author | pubmed-author:CossetFrancoi... | lld:pubmed |
| pubmed-article:16928753 | pubmed:author | pubmed-author:SchnoberEva... | lld:pubmed |
| pubmed-article:16928753 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16928753 | pubmed:volume | 80 | lld:pubmed |
| pubmed-article:16928753 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16928753 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16928753 | pubmed:pagination | 10579-90 | lld:pubmed |
| pubmed-article:16928753 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
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