Inhibition of Hepatitis C Virus-Like Particle Binding to Target Cells by Antiviral Antibodies in Acute and Chronic Hepatitis C
- 1 September 2004
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 78 (17), 9030-40
- https://doi.org/10.1128/jvi.78.17.9030-9040.2004
Abstract
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.This publication has 52 references indexed in Scilit:
- Antibody neutralization and escape by HIV-1Nature, 2003
- Hepatitis C virus–like particles combined with novel adjuvant systems enhance virus-specific immune responsesHepatology, 2003
- HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sitesNature, 2002
- Optimal therapy of hepatitis CHepatology, 2002
- Hepatitis C Virus-Like Particle MorphogenesisJournal of Virology, 2002
- Primary hepatocytes of Tupaia belangeri as a potential model for hepatitis C virus infectionJCI Insight, 2002
- Hepatitis C virus–like particles induce virus-specific humoral and cellular immune responses in miceHepatology, 2001
- Antibodies Against Hepatitis C Virus–Like Particles and Viral Clearance in Acute and Chronic Hepatitis CHepatology, 2000
- Functional Characterization of Intracellular and Secreted Forms of a Truncated Hepatitis C Virus E2 GlycoproteinJournal of Virology, 2000
- High titers of antibodies inhibiting the binding of envelope to human cells correlate with natural resolution of chronic hepatitis CHepatology, 1998