Broadly neutralizing human monoclonal antibodies to the hepatitis C virus E2 glycoprotein.
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.
Owsianka
Ania M
AM
MRC Virology Unit, Institute of Virology, University of Glasgow, Church Street, Glasgow G11 5JR, UK.
Tarr
Alexander W
AW
The Institute of Infection, Immunity and Inflammation, School of Molecular Medical Sciences, The University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
Keck
Zhen-Yong
ZY
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Li
Ta-Kai
TK
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Witteveldt
Jeroen
J
MRC Virology Unit, Institute of Virology, University of Glasgow, Church Street, Glasgow G11 5JR, UK.
Adair
Richard
R
MRC Virology Unit, Institute of Virology, University of Glasgow, Church Street, Glasgow G11 5JR, UK.
Foung
Steven K H
SKH
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ball
Jonathan K
JK
The Institute of Infection, Immunity and Inflammation, School of Molecular Medical Sciences, The University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
Patel
Arvind H
AH
MRC Virology Unit, Institute of Virology, University of Glasgow, Church Street, Glasgow G11 5JR, UK.
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
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