title: Recognition of native hepatitis C virus E1E2 heterodimers by a human monoclonal antibody.
abstract: The majority of hepatitis C virus (HCV)-infected individuals progress from acute to chronic disease, despite the presence of a strong humoral immune response to the envelope glycoproteins E1 and E2. When expressed in mammalian cells, E1 and E2 form both noncovalently linked E1E2 heterodimers, believed to be properly folded, and disulfide-linked, high-molecular-weight aggregates that are misfolded. Previously, we identified 10 human monoclonal antibodies (HMAbs) that bind E2 glycoproteins from different genotypes. Here we demonstrate that one of these HMAbs, CBH-2, is unique in its ability to distinguish between properly folded and misfolded envelope proteins. This HMAb recognizes HCV-E2 only when complexed with E1. The E1E2 complexes recognized by CBH-2 are noncovalently linked heterodimers and not misfolded disulfide-linked, high-molecular-weight aggregates. The E1E2 heterodimers seen by CBH-2 no longer associate with the endoplasmic reticulum chaperone calnexin and are likely to represent the prebudding form of the HCV virion.
authors.affiliation: Department of Medicine/Division of Oncology, Stanford University Medical Center, California 94305, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Cocquerel
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Quinn
authors.forename: Mike
authors.initials: M
authors.lastname: Flint
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Hadlock
authors.forename: Steven K H
authors.initials: SK
authors.lastname: Foung
authors.forename: Shoshana
authors.initials: S
authors.lastname: Levy
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D019281:Dimerization; D006801:Humans; D017510:Protein Folding; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; C087035:E1 protein, Hepatitis C virus; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus