Reverse epitope mapping of the E2 glycoprotein in antibody associated hepatitis C virus

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
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 > Institute of Infection Immunity and Inflammation
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656491Basis of the host range and tissue tropism for hepatitis C virusArvind PatelMedical Research Council (MRC)MC_UU_12014/2MVLS III - CENTRE FOR VIRUS RESEARCH