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Title: The involvement of oncogenic DNA viruses in Hodgkin's disease
Author: Armstrong, Alison A.
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1994
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At the outset of this project Epstein-Barr virus (EBV) was associated with a proportion of cases of Hodgkin's disease (HD). Clonal EBV genomes were detected in HD tumour material however the localisation of EBV within the malignant cells had not been clearly demonstrated. Following the availability of monoclonal antibodies to the EBV latent genes, the expression of LMP-1 and EBNA-2 was investigated in a series of HD cases. EBV LMP-1 was expressed in Reed-Sternberg (RS) cells in the majority of cases studied, however there was a lack of expression of EBNA-2. The detection of LMP-1, which has been shown to have oncogenic potential, has strengthened the evidence that EBV is involved in the pathogenesis of a proportion of HD cases. These results indicated that a distinct pattern of EBV latent gene expression, designated Lat II, was observed in HD. As LMP-1 has been shown to upregulate a number of cellular genes, the expression of CD23 and bcl-2 in HD were examined. CD23 and bcl-2 were rarely detected in RS cells. There was no correlation between LMP-1 expression and the presence of CD23 or bcl-2. These results indicate that the role of EBV in HD is independent of the upregulation of CD23 and bcl-2. Further evidence that EBV is localised to RS cells in HD was obtained following the detection of EBER RNA in RS cells using an in situ hybridisation technique. Comparison of techniques to detect EBV in HD tumour material indicated that the EBER RNA in situ hybridisation assay was the most useful and reliable method of determining EBV latent infection. We have categorised HD cases which were EBV-positive by in situ assays or using Southern blot hybridisation for the detection of clonal EBV genomes as EBV-associated. Using tine above criteria the epidemiological features of HD were investigated with respect to EBV. Paediatric HD cases, in particular cases < 10 years of age, older adults and cases of MCHD subtype were strongly EBV-associated. There was no evidence that EBV is a useful prognostic marker. Although the epidemiological features of HD suggest that young adult HD is most likely to be caused by an infectious agent our results indicated that these cases, in particular NSHD, were seldom EBV-positive. We have speculated that another virus may be involved in this age group. In order to eliminate the possibility that other known DNA viruses may be involved in HD, we examined clinical samples from HD, NHL and reactive conditions for the presence of adenovirus, SV40, LPV and HHV-7. We have not detected any of the viruses in these clinical samples. The implications of these results will be discussed further in this thesis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral