In vitro infectivity of the Hepatitis C Virus in the context of humoral immunity and immune escape

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dc.contributor.advisor Crosbie, Orla en
dc.contributor.advisor Fanning, Liam J. en
dc.contributor.advisor Kenny-Walsh, Elizabeth en Naik, Amruta S. 2017-06-14T12:02:27Z 2017-06-14T12:02:27Z 2017 2017
dc.identifier.citation Naik, A. S. 2017. In vitro infectivity of the Hepatitis C Virus in the context of humoral immunity and immune escape. PhD Thesis, University College Cork. en
dc.description.abstract The hepatitis C virus (HCV) is an enveloped virus which circulates in infected individuals as a quasispecies. HCV encodes two highly glycosylated envelope glycoproteins E1E2 which is involved in fusion and entry of the virus into the hepatocytes. E1E2 is hypervariable in nature and is a target of the humoral immune system. The humoral immune system responds to chronic HCV infection by producing neutralising antibodies (nAb). In this study, viraemic sera from chronically infected HCV individuals with genotype 1a (n=5), genotype 1b (n=12), genotype 3a (n=3) and genotype 4a (n=6) were segregated into antibody free virus (AFV) and antibody associated virus (AAV) populations. Selective targeting of clonotypic HCV variants from the quasispecies pool was documented. Furthermore, HCVpp (n=10) from a clonotypic AAV population were generated. A marked difference in the infectivity of AAV E1E2-HCVpp was observed. 40% of the psuedotyped viral particles were identified as being infectious. To assess the possible conformational or discontinuous epitope(s) outside the E1E2 gene junction, amino acid region 384-619 was selected. Five binding motifs were targeted by patient derived VF-Fab upon peptide mapping, of which two shared the residues with previously reported epitopes within CD81 binding region. One epitope lies within an immunodominant HVR1 and two were novel. Additionally, we combined VF-Fabs which have shown binding reactivity to the different epitopes to further reduce HCVpp infectivity. A significant reduction in HCVpp infectivity (p<0.05) was observed when challenged with a combination of inter genotype and subtype VF-Fabs. Our data indicates that combining the antigen specificity of different antibodies may be a useful strategy to reduce the in vitro infectivity of the HCV. en
dc.description.sponsorship Molecular Medicine Ireland (MMI-CTRSP) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2017, Amruta S. Naik. en
dc.rights.uri en
dc.subject HCV en
dc.subject Antibody associated virus en
dc.subject Epitope mapping en
dc.subject Humoral immune escape en
dc.title In vitro infectivity of the Hepatitis C Virus in the context of humoral immunity and immune escape en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral Degree (Structured) en
dc.type.qualificationname PhD (Science) en
dc.internal.availability Full text available en No embargo required en
dc.description.version Accepted Version
dc.contributor.funder Molecular Medicine Ireland en
dc.contributor.funder University College Cork en
dc.description.status Not peer reviewed en Medicine en
dc.check.type No Embargo Required
dc.check.reason No embargo required en
dc.check.opt-out Not applicable en
dc.thesis.opt-out false
dc.check.embargoformat Not applicable en
dc.internal.conferring Autumn 2017 en

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© 2017, Amruta S. Naik. Except where otherwise noted, this item's license is described as © 2017, Amruta S. Naik.
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