title: Broadly neutralizing human monoclonal antibodies to the hepatitis C virus E2 glycoprotein.
abstract: The humoral response to hepatitis C virus (HCV) may contribute to controlling infection. We previously isolated human monoclonal antibodies to conformational epitopes on the HCV E2 glycoprotein. Here, we report on their ability to inhibit infection by retroviral pseudoparticles incorporating a panel of full-length E1E2 clones representing the full spectrum of genotypes 1-6. We identified one antibody, CBH-5, that was capable of neutralizing every genotype tested. It also potently inhibited chimeric cell culture-infectious HCV, which had genotype 2b envelope proteins in a genotype 2a (JFH-1) background. Analysis using a panel of alanine-substitution mutants of HCV E2 revealed that the epitope of CBH-5 includes amino acid residues that are required for binding of E2 to CD81, a cellular receptor essential for virus entry. This suggests that CBH-5 inhibits HCV infection by competing directly with CD81 for a binding site on E2.
authors.affiliation: MRC Virology Unit, Institute of Virology, University of Glasgow, Church Street, Glasgow G11 5JR, UK.
authors.forename: Ania M
authors.initials: AM
authors.lastname: Owsianka
authors.affiliation: The Institute of Infection, Immunity and Inflammation, School of Molecular Medical Sciences, The University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Tarr
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Zhen-Yong
authors.initials: ZY
authors.lastname: Keck
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Ta-Kai
authors.initials: TK
authors.lastname: Li
authors.affiliation: MRC Virology Unit, Institute of Virology, University of Glasgow, Church Street, Glasgow G11 5JR, UK.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Witteveldt
authors.affiliation: MRC Virology Unit, Institute of Virology, University of Glasgow, Church Street, Glasgow G11 5JR, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Adair
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Steven K H
authors.initials: SKH
authors.lastname: Foung
authors.affiliation: The Institute of Infection, Immunity and Inflammation, School of Molecular Medical Sciences, The University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Ball
authors.affiliation: MRC Virology Unit, Institute of Virology, University of Glasgow, Church Street, Glasgow G11 5JR, UK.
authors.forename: Arvind H
authors.initials: AH
authors.lastname: Patel
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD; D002460:Cell Line; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D018937:Hepatitis C Antibodies / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests; D012190:Retroviridae / Q000235:genetics / Q000276:immunology; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014771:Virion / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C554798:CD81 protein, human; D000939:Epitopes; D018937:Hepatitis C Antibodies; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus