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

Michelle C. Sabo, Vincent C. Luca, Stuart Campbell Ray, Jens Bukh, Daved H. Fremont, Michael S. Diamond

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)174-184
Number of pages11
JournalVirology
Volume422
Issue number2
DOIs
StatePublished - Jan 20 2012

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Hepacivirus
Epitopes
Temperature
Antibodies
Virion
Flavivirus
Apolipoproteins
Polysaccharides
Monoclonal Antibodies
Serum
Proteins

Keywords

  • Antibody
  • Hepatitis C
  • Neutralization
  • Structure
  • Virion

ASJC Scopus subject areas

  • Virology

Cite this

Hepatitis C virus epitope exposure and neutralization by antibodies is affected by time and temperature. / Sabo, Michelle C.; Luca, Vincent C.; Ray, Stuart Campbell; Bukh, Jens; Fremont, Daved H.; Diamond, Michael S.

In: Virology, Vol. 422, No. 2, 20.01.2012, p. 174-184.

Research output: Contribution to journalArticle

Sabo, Michelle C. ; Luca, Vincent C. ; Ray, Stuart Campbell ; Bukh, Jens ; Fremont, Daved H. ; Diamond, Michael S. / Hepatitis C virus epitope exposure and neutralization by antibodies is affected by time and temperature. In: Virology. 2012 ; Vol. 422, No. 2. pp. 174-184.
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