title: Immunogenic and functional organization of hepatitis C virus (HCV) glycoprotein E2 on infectious HCV virions.
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 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 microg/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.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Zhen-Yong
authors.initials: ZY
authors.lastname: Keck
authors.forename: Jinming
authors.initials: J
authors.lastname: Xia
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Cai
authors.forename: Ta-Kai
authors.initials: TK
authors.lastname: Li
authors.forename: Ania M
authors.initials: AM
authors.lastname: Owsianka
authors.forename: Arvind H
authors.initials: AH
authors.lastname: Patel
authors.forename: Guangxiang
authors.initials: G
authors.lastname: Luo
authors.forename: Steven K H
authors.initials: SK
authors.lastname: Foung
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D018937:Hepatitis C Antibodies / Q000276:immunology; D006801:Humans; D009500:Neutralization Tests; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D014771:Virion / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*
chemical_list: D015703:Antigens, CD; C554798:CD81 protein, human; D018937:Hepatitis C Antibodies; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus