A Neutralization Epitope in the Hepatitis C Virus E2 Glycoprotein Interacts with Host Entry Factor CD81

• Type of Material: Article
• Authors: Zhong Zhao, Food and Drug Administration; Lilin Zhong, Food and Drug Administration; Elizabeth Elrod, Emory University; Evi Struble, Food and Drug Administration; Li Ma, Food and Drug Administration; Hailing Yan, Food and Drug Administration; Christine Harman, Food and Drug Administration; Lu Deng, Food and Drug Administration; Maria Luisa Virata-Theimer, Food and Drug Administration; Peter Liu, Food and Drug Administration; Harvey Alter, National Institutes of Health; Arash Grakoui, Emory University; Pei Zhang, Food and Drug Administration
• Language: English
• Date: 2014-01-06
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
• License: Creative Commons Universal : Public Domain Dedication
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0084346
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 9
• Issue: 1
• Start Page: e84346
• End Page: e84346
• Grant/Funding Information: This study was supported by the Modernizing Science Funds of the Food and Drug Administration.
• Keywords: ENVELOPE GLYCOPROTEIN; PARTICLES; RECEPTOR; PLASMA; PROGRESS; Multidisciplinary Sciences; INFECTION; BINDING; GENOTYPES; Science & Technology - Other Topics; VIRAL ENTRY; Science & Technology; ANTIBODIES
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Immunology

Abstract

The identification of a specific immunogenic candidate that will effectively activate the appropriate pathway for neutralizing antibody production is fundamental for vaccine design. By using a monoclonal antibody (1H8) that neutralizes HCV in vitro, we have demonstrated here that 1H8 recognized an epitope mapped between residues A524 and W529 of the E2 protein. We also found that the epitope residues A524, P525, Y527 and W529 were crucial for antibody binding, while the residues T526, Y527 and W529 within the same epitope engaged in the interaction with the host entry factor CD81. Furthermore, we detected "1H8-like" antibodies, defined as those with amino acid-specificity similar to 1H8, in the plasma of patients with chronic HCV infection. The time course study of plasma samples from Patient H, a well-characterized case of posttransfusion hepatitis C, showed that "1H8-like" antibodies could be detected in a sample collected almost two years after the initial infection, thus confirming the immunogenicity of this epitope in vivo. The characterization of this neutralization epitope with a function in host entry factor CD81 interaction should enhance our understanding of antibody-mediated neutralization of HCV infections.