Reverse epitope mapping of the E2 glycoprotein in antibody associated hepatitis C virus.
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...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0175349&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850133352810545152 |
|---|---|
| author | Amruta S Naik Ania Owsianka Brendan A Palmer Ciaran J O'Halloran Nicole Walsh Orla Crosbie Elizabeth Kenny-Walsh Arvind H Patel Liam J Fanning |
| author_facet | Amruta S Naik Ania Owsianka Brendan A Palmer Ciaran J O'Halloran Nicole Walsh Orla Crosbie Elizabeth Kenny-Walsh Arvind H Patel Liam J Fanning |
| author_sort | Amruta S Naik |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7c0920706b6d4cb28d45f68a59c79b59 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-7c0920706b6d4cb28d45f68a59c79b592025-08-20T02:31:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01125e017534910.1371/journal.pone.0175349Reverse epitope mapping of the E2 glycoprotein in antibody associated hepatitis C virus.Amruta S NaikAnia OwsiankaBrendan A PalmerCiaran J O'HalloranNicole WalshOrla CrosbieElizabeth Kenny-WalshArvind H PatelLiam J FanningThe 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0175349&type=printable |
| spellingShingle | Amruta S Naik Ania Owsianka Brendan A Palmer Ciaran J O'Halloran Nicole Walsh Orla Crosbie Elizabeth Kenny-Walsh Arvind H Patel Liam J Fanning Reverse epitope mapping of the E2 glycoprotein in antibody associated hepatitis C virus. PLoS ONE |
| title | Reverse epitope mapping of the E2 glycoprotein in antibody associated hepatitis C virus. |
| title_full | Reverse epitope mapping of the E2 glycoprotein in antibody associated hepatitis C virus. |
| title_fullStr | Reverse epitope mapping of the E2 glycoprotein in antibody associated hepatitis C virus. |
| title_full_unstemmed | Reverse epitope mapping of the E2 glycoprotein in antibody associated hepatitis C virus. |
| title_short | Reverse epitope mapping of the E2 glycoprotein in antibody associated hepatitis C virus. |
| title_sort | reverse epitope mapping of the e2 glycoprotein in antibody associated hepatitis c virus |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0175349&type=printable |
| work_keys_str_mv | AT amrutasnaik reverseepitopemappingofthee2glycoproteininantibodyassociatedhepatitiscvirus AT aniaowsianka reverseepitopemappingofthee2glycoproteininantibodyassociatedhepatitiscvirus AT brendanapalmer reverseepitopemappingofthee2glycoproteininantibodyassociatedhepatitiscvirus AT ciaranjohalloran reverseepitopemappingofthee2glycoproteininantibodyassociatedhepatitiscvirus AT nicolewalsh reverseepitopemappingofthee2glycoproteininantibodyassociatedhepatitiscvirus AT orlacrosbie reverseepitopemappingofthee2glycoproteininantibodyassociatedhepatitiscvirus AT elizabethkennywalsh reverseepitopemappingofthee2glycoproteininantibodyassociatedhepatitiscvirus AT arvindhpatel reverseepitopemappingofthee2glycoproteininantibodyassociatedhepatitiscvirus AT liamjfanning reverseepitopemappingofthee2glycoproteininantibodyassociatedhepatitiscvirus |