A point mutation leading to hepatitis C virus escape from neutralization by a monoclonal antibody to a conserved conformational epitope

Keck, Z.Y., Olson, O., Gal-Tanamy, M., Xia, J., Patel, A.H. , Dreux, M., Cosset, F.L., Lemon, S.M. and Foung, S.K.H. (2008) A point mutation leading to hepatitis C virus escape from neutralization by a monoclonal antibody to a conserved conformational epitope. Journal of Virology, 82(12), pp. 6067-6072. (doi:10.1128/JVI.00252-08) (PMID:18385242) (PMCID:PMC2395135)

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Abstract

A challenge in hepatitis C virus vaccine development is defining conserved protective epitopes. A cluster of these epitopes comprises an immunodominant domain on the E2 glycoprotein, designated domain B. CBH-2 is a neutralizing human monoclonal antibody to a domain B epitope that is highly conserved. Alanine scanning demonstrated that the epitope involves residues G523, G530 and D535 that are also contact residues for E2 binding to CD81, a co-receptor required for virus entry into cells. However, another residue, located at position 431 and thus at a considerable distance in the linear sequence of E2, also contributes to the CBH-2 epitope. A single amino acid substitution at this residue results in escape from CBH-2-mediated neutralization in a genotype 1a virus. These results highlight the challenges inherent in developing HCV vaccines, and show that an effective vaccine will need to induce antibodies to both conserved as well as more invariant epitopes to minimize virus escape

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Patel, Professor Arvind
Authors: Keck, Z.Y., Olson, O., Gal-Tanamy, M., Xia, J., Patel, A.H., Dreux, M., Cosset, F.L., Lemon, S.M., and Foung, S.K.H.
Subjects:Q Science > QR Microbiology > QR355 Virology
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Virology
Journal Abbr.:J. Virol.
ISSN:0022-538X
ISSN (Online):1098-5514
Published Online:02 April 2008

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