Hepatitis C virus epitope exposure and neutralization by antibodies is affected by time and temperature

TY - JOUR

T1 - Hepatitis C virus epitope exposure and neutralization by antibodies is affected by time and temperature

AU - Sabo, Michelle C

AU - Luca, Vincent C

AU - Ray, Stuart C

AU - Bukh, Jens

AU - Fremont, Daved H

AU - Diamond, Michael S

N1 - Copyright © 2011 Elsevier Inc. All rights reserved.

PY - 2012/1/20

Y1 - 2012/1/20

N2 - 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.

AB - 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.

KW - Antibodies, Monoclonal

KW - Binding Sites, Antibody

KW - Cell Line

KW - Epitopes

KW - Hepacivirus

KW - Hepatitis C

KW - Hepatitis C Antibodies

KW - Humans

KW - Kinetics

KW - Temperature

KW - Time Factors

U2 - 10.1016/j.virol.2011.10.023

DO - 10.1016/j.virol.2011.10.023

M3 - Journal article

C2 - 22078164

SN - 0042-6822

VL - 422

SP - 174

EP - 184

JO - Virology

JF - Virology

IS - 2

ER -