Inhibition of hepatitis C virus-like particle binding to target cells by antiviral antibodies in acute and chronic hepatitis C

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, Geneviéve Inchauspé, T. Jake Liang, Hubert E. Blum, Thomas F. Baumert

Research output: Contribution to journalArticle

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 (SQKIQLVN TNGSWHI; 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.

Original languageEnglish (US)
Pages (from-to)9030-9040
Number of pages11
JournalJournal of Virology
Volume78
Issue number17
DOIs
StatePublished - Sep 2004
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Steinmann, D., Barth, H., Gissler, B., Schürmann, P., Adah, M. I., Gerlach, J. T., Pape, G. R., Depla, E., Jacobs, D., Maertens, G., Patel, A. H., Inchauspé, G., Liang, T. J., Blum, H. E., & Baumert, T. F. (2004). Inhibition of hepatitis C virus-like particle binding to target cells by antiviral antibodies in acute and chronic hepatitis C. Journal of Virology, 78(17), 9030-9040. https://doi.org/10.1128/JVI.78.17.9030-9040.2004