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Journal of Virology, January 2003, p. 1604-1609, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.1604-1609.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Recognition of Native Hepatitis C Virus E1E2 Heterodimers by a Human Monoclonal Antibody

Laurence Cocquerel,1 Elizabeth R. Quinn,1 Mike Flint,1 Kenneth G. Hadlock,2 Steven K. H. Foung,2 and Shoshana Levy1*

Departments of Medicine/Division of Oncology,1 Pathology, Stanford University Medical Center, Stanford, California 943052

Received 20 August 2002/ Accepted 10 October 2002

The majority of hepatitis C virus (HCV)-infected individuals progress from acute to chronic disease, despite the presence of a strong humoral immune response to the envelope glycoproteins E1 and E2. When expressed in mammalian cells, E1 and E2 form both noncovalently linked E1E2 heterodimers, believed to be properly folded, and disulfide-linked, high-molecular-weight aggregates that are misfolded. Previously, we identified 10 human monoclonal antibodies (HMAbs) that bind E2 glycoproteins from different genotypes. Here we demonstrate that one of these HMAbs, CBH-2, is unique in its ability to distinguish between properly folded and misfolded envelope proteins. This HMAb recognizes HCV-E2 only when complexed with E1. The E1E2 complexes recognized by CBH-2 are noncovalently linked heterodimers and not misfolded disulfide-linked, high-molecular-weight aggregates. The E1E2 heterodimers seen by CBH-2 no longer associate with the endoplasmic reticulum chaperone calnexin and are likely to represent the prebudding form of the HCV virion.


* Corresponding author. Mailing address: Department of Medicine, Division of Oncology, Stanford University Medical Center, 1105a North Wing, CCSR Building, 269 Campus Dr., Stanford, CA 94305-5151. Phone: (650) 725-6425. Fax: (650) 725-1420. E-mail: levy{at}cmgm.stanford.edu.


Journal of Virology, January 2003, p. 1604-1609, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.1604-1609.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.