title: Hepatitis C virus epitope exposure and neutralization by antibodies is affected by time and temperature.
abstract: A recent study with flaviviruses suggested that structural dynamics of the virion impact antibody neutralization via exposure of ostensibly cryptic epitopes. To determine whether this holds true for the distantly related hepatitis C virus (HCV), whose neutralizing epitopes may be obscured by a glycan shield, apolipoprotein interactions, and the hypervariable region on the E2 envelope protein, we assessed how time and temperature of pre-incubation altered monoclonal antibody (MAb) neutralization of HCV. Notably, several MAbs showed increased inhibitory activity when pre-binding was performed at 37°C or after longer pre-incubation periods, and a corresponding loss-of-neutralization was observed when pre-binding was performed at 4°C. A similar profile of changes was observed with acute and chronic phase sera from HCV-infected patients. Our data suggest that time and temperature of incubation modulate epitope exposure on the conformational ensembles of HCV virions and thus, alter the potency of antibody neutralization.
authors.affiliation: Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Sabo
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Luca
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Ray
authors.forename: Jens
authors.initials: J
authors.lastname: Bukh
authors.forename: Daved H
authors.initials: DH
authors.lastname: Fremont
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D001666:Binding Sites, Antibody; D002460:Cell Line; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006526:Hepatitis C / Q000097:blood; D018937:Hepatitis C Antibodies / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D013696:Temperature; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D018937:Hepatitis C Antibodies
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