Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.796110
Title: Tumour antigens and herpes simplex virus oncogenesis
Author: Hewitt, Robert Edwin Patrick
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1988
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Abstract:
Herpes simplex virus (HSV) has been implicated in the aetiology of human cervical cancer, but despite intensive investigation the oncogenic properties of HSV are still not well understood. Studies reported here, explore one possible molecular mechanism by which this virus may cause oncogenic transformation; namely, the induction of cellular polypeptides which play a role in oncogenesis. A group of cellular polypeptides specific to cells showing the immortalized phenotype were previously detected in a range of cell lines, including the Bn5T cell line which is derived from rat embryo fibroblasts transformed by a fragment of the HSV type 2 (HSV-2) genome. These polypeptides which will be referred to as Bn5T:TBS polypeptides, are not detectable in control rat embryo fibroblasts. Bn5T:TBS polypeptides are immunoprecipitated by tumour bearing serum (TBS) and studies presented in this thesis confirm that they are also immunoprecipitated by the monoclonal antibody TG7A. The TG7A monoclonal was raised against affinity purified DNA binding proteins from HSV-2 infected cells and recognizes cellular polypeptides induced on infection by the virus. This suggests that Bn5T:TBS polypeptides are related to polypeptides induced in HSV-2 infection. Another feature of Bn5T:TBS polypeptides is that they all show oncofoetal expression, suggesting that they have a physiological role in cell proliferation and differentiation. Members of the Bn5T:TBS set have always been found to be either co-expressed or not expressed at all, in a range of different cell types and culture conditions. This suggests that these polypeptides may have a common precursor or be induced by the same factor(s) and it also suggests that they may have a common function. Three of the six members of the Bn5T:TBS set give similar peptide maps, suggesting that they possess similar or shared domains. In addition, pulse labelling and pulse-chase labelling experiments suggest that at least two members of the set result from post-translational processing events. Immunological and peptide mapping studies indicate that a Bn5T:TBS polypeptide of 97kDa molecular weight, is related to the 90kDa heat shock protein (HSP90) and that it may share a domain with an HSV-2-induced form of HSP90. The TG7A monoclonal recognizes a highly conserved epitope present on a bacterial heat-shock protein, an HSV-2-induced 90kDa polypeptide (also recognized by a monoclonal against HSP90) and a 97kDa transformed cell polypeptide belonging to the Bn5T:TBS set. These findings suggest that an HSV-2-induced form of the HSP90 may play a role in oncogenic transformation by the virus. The synthesis of Bn5T:TBS polypeptides has not been detected in the rabbit reticulocyte lysate in vitro translation system and possible reasons for this have been investigated. Further, data from an amino acid sequencing study suggests that the 97kDa polypeptide in the Bn5T:TBS set has a domain with homology to one form of bovine casein; likely explanations are discussed in detail.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.796110  DOI: Not available
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