This Article Full Text (PDF) Other Versions of this Article: JVI.01710-06v1 81/2/1043    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Keck, Z.-Y. Articles by Foung, S. K.H. Search for Related Content PubMed PubMed Citation Articles by Keck, Z.-Y. Articles by Foung, S. K.H.

 Previous Article  |  Next Article 

J. Virol. doi:10.1128/JVI.01710-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Immunogenic and Functional Organization of Hepatitis C virus (HCV) Glycoprotein E2 on Infectious HCV Virions

Department of Pathology, Stanford University School of Medicine, Stanford CA 94305; Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Ky 40536; MRC Virology Unit, Institute of Virology, University of Glasgow, Church Street, Glasgow G11 5JR, UK

^* To whom correspondence should be addressed. Email: sfoung{at}stanford.edu.

	Abstract

Development of full-length hepatitis C virus (HCV) RNAs replicating efficiently and producing infectious cell-cultured virions, HCVcc, in hepatoma cells provides an opportunity to characterize immunogenic domains on viral envelope proteins involved in entry to target cells. A panel of IgG₁ human monoclonal antibodies (HMAbs) to three immunogenic conformational domains (designated A, B and C) on HCV E2 glycoprotein showed that epitopes within two domains, B and C, mediated HCVcc neutralization, whereas HMAbs to domain A were all nonneutralizing. For the neutralizing antibodies to domain B (with some to conserved epitopes among different HCV genotypes), the inhibitory antibody concentration reducing HCVcc infection by 90%, IC₉₀, ranged from 0.1-4 µg/ml. For some neutralizing HMAbs, HCVcc neutralization displayed a linear correlation with antibody concentration between IC₅₀ and IC₉₀ while others showed a nonlinear correlation. The differences in IC₅₀/IC₉₀ ratios with earlier findings that neutralizing HMAbs block E2 interaction with CD81 suggests that these antibodies block different facets of virus-receptor interaction. Collectively, these findings support an immunogenic model of HCV E2 having three immunogenic domains with distinct structures and functions, and provide added support that CD81 is required for virus entry.

This article has been cited by other articles:

• Keck, Z.-Y., Olson, O., Gal-Tanamy, M., Xia, J., Patel, A. H., Dreux, M., Cosset, F.-L., Lemon, S. M., Foung, S. K. H. (2008). A Point Mutation Leading to Hepatitis C Virus Escape from Neutralization by a Monoclonal Antibody to a Conserved Conformational Epitope. J. Virol. 82: 6067-6072 [Abstract] [Full Text]  
• Keck, Z.-Y., Li, T.-K., Xia, J., Gal-Tanamy, M., Olson, O., Li, S. H., Patel, A. H., Ball, J. K., Lemon, S. M., Foung, S. K. H. (2008). Definition of a Conserved Immunodominant Domain on Hepatitis C Virus E2 Glycoprotein by Neutralizing Human Monoclonal Antibodies. J. Virol. 82: 6061-6066 [Abstract] [Full Text]  
• Owsianka, A. M., Tarr, A. W., Keck, Z.-Y., Li, T.-K., Witteveldt, J., Adair, R., Foung, S. K. H., Ball, J. K., Patel, A. H. (2008). Broadly neutralizing human monoclonal antibodies to the hepatitis C virus E2 glycoprotein. J. Gen. Virol. 89: 653-659 [Abstract] [Full Text]  
• Meyer, K., Ait-Goughoulte, M., Keck, Z.-Y., Foung, S., Ray, R. (2008). Antibody-Dependent Enhancement of Hepatitis C Virus Infection. J. Virol. 82: 2140-2149 [Abstract] [Full Text]  
• Perotti, M., Mancini, N., Diotti, R. A., Tarr, A. W., Ball, J. K., Owsianka, A., Adair, R., Patel, A. H., Clementi, M., Burioni, R. (2008). Identification of a Broadly Cross-Reacting and Neutralizing Human Monoclonal Antibody Directed against the Hepatitis C Virus E2 Protein. J. Virol. 82: 1047-1052 [Abstract] [Full Text]  
• Chang, K.-S., Jiang, J., Cai, Z., Luo, G. (2007). Human Apolipoprotein E Is Required for Infectivity and Production of Hepatitis C Virus in Cell Culture. J. Virol. 81: 13783-13793 [Abstract] [Full Text]  
• McCaffrey, K., Boo, I., Poumbourios, P., Drummer, H. E. (2007). Expression and Characterization of a Minimal Hepatitis C Virus Glycoprotein E2 Core Domain That Retains CD81 Binding. J. Virol. 81: 9584-9590 [Abstract] [Full Text]  
• Helle, F., Goffard, A., Morel, V., Duverlie, G., McKeating, J., Keck, Z.-Y., Foung, S., Penin, F., Dubuisson, J., Voisset, C. (2007). The Neutralizing Activity of Anti-Hepatitis C Virus Antibodies Is Modulated by Specific Glycans on the E2 Envelope Protein. J. Virol. 81: 8101-8111 [Abstract] [Full Text]