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Journal of Virology, January 2007, p. 1043-1047, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01710-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Immunogenic and Functional Organization of Hepatitis C Virus (HCV) Glycoprotein E2 on Infectious HCV Virions{triangledown}

Zhen-Yong Keck,1 Jinming Xia,1 Zhaohui Cai,2 Ta-Kai Li,1 Ania M. Owsianka,3 Arvind H. Patel,3 Guangxiang Luo,2 and Steven K. H. Foung1*

Department of Pathology, Stanford University School of Medicine, Stanford, California 94305,1 Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky 40536,2 MRC Virology Unit, Institute of Virology, University of Glasgow, Church Street, Glasgow G11 5JR, United Kingdom3

Received 8 August 2006/ Accepted 23 October 2006

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 into target cells. A panel of immunoglobulin G1 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 to 4 µg/ml. For some neutralizing HMAbs, HCVcc neutralization displayed a linear correlation with an antibody concentration between the IC50 and the IC90 while others showed a nonlinear correlation. The differences between IC50/IC90 ratios and earlier findings that neutralizing HMAbs block E2 interaction with CD81 suggest 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 for the idea that CD81 is required for virus entry.

* Corresponding author. Mailing address: Stanford Medical School Blood Center, 800 Welch Rd., Palo Alto, CA 94304. Phone: (650) 723-6481. Fax: (650) 498-6283. E-mail: sfoung{at}stanford.edu.

{triangledown} Published ahead of print on 1 November 2006.

Journal of Virology, January 2007, p. 1043-1047, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01710-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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