title: Human monoclonal antibody to hepatitis C virus E1 glycoprotein that blocks virus attachment and viral infectivity.
abstract: Human antibodies elicited in response to hepatitis C virus (HCV) infection are anticipated to react with the native conformation of the viral envelope structure. Isolation of these antibodies as human monoclonal antibodies that block virus binding and entry will be useful in providing potential therapeutic reagents and for vaccine development. H-111, an antibody to HCV envelope 1 protein (E1) that maps to the YEVRNVSGVYH sequence and is located near the N terminus of E1 and is able to immunoprecipitate E1E2 heterodimers, is described. Binding of H-111 to HCV E1 genotypes 1a, 1b, 2b, and 3a indicates that the H-111 epitope is highly conserved. Sequence analysis of antibody V regions showed evidence of somatic and affinity maturation of H-111. Finally, H-111 blocks HCV-like particle binding to and HCV virion infection of target cells, suggesting the involvement of this epitope in virus binding and entry.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, CA 94305, USA.
authors.forename: Zhen-Yong
authors.initials: ZY
authors.lastname: Keck
authors.forename: Vicky M H
authors.initials: VM
authors.lastname: Sung
authors.forename: Susan
authors.initials: S
authors.lastname: Perkins
authors.forename: Judy
authors.initials: J
authors.lastname: Rowe
authors.forename: Sudhir
authors.initials: S
authors.lastname: Paul
authors.forename: T Jake
authors.initials: TJ
authors.lastname: Liang
authors.forename: Michael M C
authors.initials: MM
authors.lastname: Lai
authors.forename: Steven K H
authors.initials: SK
authors.lastname: Foung
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology*; D001402:B-Lymphocytes; D002460:Cell Line; D018604:Epitope Mapping; D016174:Hepacivirus / Q000276:immunology* / Q000472:pathogenicity* / Q000502:physiology; D018937:Hepatitis C Antibodies / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; C087035:E1 protein, Hepatitis C virus; D018937:Hepatitis C Antibodies; D014759:Viral Envelope Proteins