| Neutralizing antibody-resistant hepatitis C virus cell-to-cell transmission. | |
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MedLine Citation:
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PMID: 20962076 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hepatitis C virus (HCV) can initiate infection by cell-free particle and cell-cell contact-dependent transmission. In this study we use a novel infectious coculture system to examine these alternative modes of infection. Cell-to-cell transmission is relatively resistant to anti-HCV glycoprotein monoclonal antibodies and polyclonal immunoglobulin isolated from infected individuals, providing an effective strategy for escaping host humoral immune responses. Chimeric viruses expressing the structural proteins representing the seven major HCV genotypes demonstrate neutralizing antibody-resistant cell-to-cell transmission. HCV entry is a multistep process involving numerous receptors. In this study we demonstrate that, in contrast to earlier reports, CD81 and the tight-junction components claudin-1 and occludin are all essential for both cell-free and cell-to-cell viral transmission. However, scavenger receptor BI (SR-BI) has a more prominent role in cell-to-cell transmission of the virus, with SR-BI-specific antibodies and small-molecule inhibitors showing preferential inhibition of this infection route. These observations highlight the importance of targeting host cell receptors, in particular SR-BI, to control viral infection and spread in the liver. |
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Authors:
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Claire L Brimacombe; Joe Grove; Luke W Meredith; Ke Hu; Andrew J Syder; Maria Victoria Flores; Jennifer M Timpe; Sophie E Krieger; Thomas F Baumert; Timothy L Tellinghuisen; Flossie Wong-Staal; Peter Balfe; Jane A McKeating |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-20 |
Journal Detail:
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Title: Journal of virology Volume: 85 ISSN: 1098-5514 ISO Abbreviation: J. Virol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-14 Completed Date: 2011-01-20 Revised Date: 2011-07-20 |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: United States |
Other Details:
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Languages: eng Pagination: 596-605 Citation Subset: IM |
Affiliation:
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Hepatitis C Research Group, Institute For Biomedical Research, University of Birmingham, Vincent Drive, Birmingham B15 2TT, United Kingdom. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antibodies, Neutralizing
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immunology* Antigens, CD / genetics, metabolism Cell Line, Tumor Coculture Techniques Hepacivirus / immunology, metabolism, physiology* Hepatitis C Antibodies / immunology* Humans Membrane Proteins / genetics, metabolism Receptors, Virus / genetics, metabolism Scavenger Receptors, Class B / genetics, metabolism* Tight Junctions / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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AI40034/AI/NIAID NIH HHS; AI50798/AI/NIAID NIH HHS; G0400802//Medical Research Council; R01 DA024565/DA/NIDA NIH HHS; //Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Neutralizing; 0/Antigens, CD; 0/CD81 antigen; 0/Hepatitis C Antibodies; 0/Membrane Proteins; 0/Receptors, Virus; 0/Scavenger Receptors, Class B; 0/claudin 1; 0/occludin |
| Comments/Corrections | |
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