Naik, A. S., Owsianka, A., Palmer, B. A., Halloran, C. J., Walsh, N., Crosbie, O., Kenny-Walsh, E., Patel, A. H. and Fanning, L. J. (2017) Reverse epitope mapping of the E2 glycoprotein in antibody associated hepatitis C virus. PLoS ONE, 12(5), e0175349. (doi: 10.1371/journal.pone.0175349) (PMID:28558001) (PMCID:PMC5448734)
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Abstract
The humoral immune system responds to chronic hepatitis C virus (HCV) infection by producing neutralising antibodies (nAb). In this study we generated three HCV pseudoparticles in which E1E2 glycoprotein sequence was targeted by the host humoral immune system. We used patient derived virus free Fabs (VF-Fabs) obtained from HCV genotype 1a (n = 3), genotype 1b (n = 7) and genotype 3a (n = 1) for neutralisation of HCVpp produced in this study both individually and in combination. Based on the available anti-HCV monoclonal nAb mapping information we selected amino acid region 384–619 for conformational epitope mapping. Amongst our notable findings, we observed significant reduction in HCVpp infectivity (p<0.05) when challenged with a combination of inter genotype and subtype VF-Fabs. We also identified five binding motifs targeted by patient derived VF-Fab upon peptide mapping, of which two shared the residues with previously reported epitopes. One epitope lies within an immunodominant HVR1 and two were novel. In summary, we used a reverse epitope mapping strategy to identify preferred epitopes by the host humoral immune system. Additionally, we have combined different VF-Fabs to further reduce the HCVpp infectivity. Our data indicates that combining the antigen specificity of antibodies may be a useful strategy to reduce (in-vitro) infectivity.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Owsianka, Dr Anna and Patel, Professor Arvind |
Authors: | Naik, A. S., Owsianka, A., Palmer, B. A., Halloran, C. J., Walsh, N., Crosbie, O., Kenny-Walsh, E., Patel, A. H., and Fanning, L. J. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
Journal Name: | PLoS ONE |
Publisher: | Public Library of Science |
ISSN: | 1932-6203 |
ISSN (Online): | 1932-6203 |
Copyright Holders: | Copyright © 2017 Naik et al. |
First Published: | First published in PLoS ONE 12(5):e0175349 |
Publisher Policy: | Reproduced under a Creative Commons License |
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