title: A neutralization epitope in the hepatitis C virus E2 glycoprotein interacts with host entry factor CD81.
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 post-transfusion 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.
authors.affiliation: Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States of America.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States of America.
authors.forename: Lilin
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Emory Vaccine Center, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Elrod
authors.affiliation: Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States of America.
authors.forename: Evi
authors.initials: E
authors.lastname: Struble
authors.affiliation: Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States of America.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States of America.
authors.forename: Hailing
authors.initials: H
authors.lastname: Yan
authors.affiliation: Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States of America.
authors.forename: Christine
authors.initials: C
authors.lastname: Harman
authors.affiliation: Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States of America.
authors.forename: Lu
authors.initials: L
authors.lastname: Deng
authors.affiliation: Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States of America.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Virata-Theimer
authors.affiliation: Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Transfusion Medicine, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Harvey
authors.initials: H
authors.lastname: Alter
authors.affiliation: Emory Vaccine Center, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Arash
authors.initials: A
authors.lastname: Grakoui
authors.affiliation: Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States of America.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D057134:Antibodies, Neutralizing / Q000276:immunology; D001665:Binding Sites; D017124:Conserved Sequence; D000939:Epitopes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000378:metabolism*; D018937:Hepatitis C Antibodies / Q000276:immunology; D006801:Humans; D011485:Protein Binding / Q000276:immunology; D060225:Tetraspanin 28 / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D018937:Hepatitis C Antibodies; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus