Document Detail


Inhibition of hepatitis C virus-like particle binding to target cells by antiviral antibodies in acute and chronic hepatitis C.
MedLine Citation:
PMID:  15308699     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hepatitis C virus (HCV) is a leading cause of chronic viral hepatitis worldwide. The study of antibody-mediated virus neutralization has been hampered by the lack of an efficient and high-throughput cell culture system for the study of virus neutralization. The HCV structural proteins have been shown to assemble into noninfectious HCV-like particles (HCV-LPs). Similar to serum-derived virions, HCV-LPs bind and enter human hepatocytes and hepatoma cell lines. In this study, we developed an HCV-LP-based model system for a systematic functional analysis of antiviral antibodies from patients with acute or chronic hepatitis C. We demonstrate that cellular HCV-LP binding was specifically inhibited by antiviral antibodies from patients with acute or chronic hepatitis C in a dose-dependent manner. Using a library of homologous overlapping envelope peptides covering the entire HCV envelope, we identified an epitope in the N-terminal E2 region (SQKIQLVNTNGSWHI; amino acid positions 408 to 422) as one target of human antiviral antibodies inhibiting cellular particle binding. Using a large panel of serum samples from patients with acute and chronic hepatitis C, we demonstrated that the presence of antibodies with inhibition of binding activity was not associated with viral clearance. In conclusion, antibody-mediated inhibition of cellular HCV-LP binding represents a convenient system for the functional characterization of human anti-HCV antibodies, allowing the mapping of envelope neutralization epitopes targeted by naturally occurring antiviral antibodies.
Authors:
Daniel Steinmann; Heidi Barth; Bettina Gissler; Peter Schürmann; Mohammed I Adah; J Tilman Gerlach; Gerd R Pape; Erik Depla; Dirk Jacobs; Geert Maertens; Arvind H Patel; Geneviève Inchauspé; T Jake Liang; Hubert E Blum; Thomas F Baumert
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of virology     Volume:  78     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-08-13     Completed Date:  2004-09-16     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9030-40     Citation Subset:  IM    
Affiliation:
Department of Medicine II, University of Freiburg, Freiburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Cell Line, Tumor
Epitope Mapping
Hepacivirus / classification,  immunology*,  physiology*
Hepatitis C / immunology*,  virology*
Hepatitis C Antibodies / immunology*
Hepatitis C, Chronic / immunology*,  virology*
Humans
Immune Sera / immunology
Viral Envelope Proteins / antagonists & inhibitors,  immunology,  metabolism
Virion / classification,  immunology,  metabolism
Chemical
Reg. No./Substance:
0/Hepatitis C Antibodies; 0/Immune Sera; 0/Viral Envelope Proteins
Comments/Corrections

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