Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.398336
Title: Viral and host gene expression in human B-cell lymphoma
Author: Jenner, Richard Gareth
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2002
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Abstract:
Kaposi's sarcoma-associated herpesvirus (KSHV) was discovered in 1994 in Kaposi's sarcoma and has since fulfilled all criteria for causation. KSHV is also associated with two forms of B-cell neoplasia; primary effusion lymphoma (PEL) and plasmablastic multicentric Castleman's disease (MCD). In most instances, PEL is thought to derive from a post-germinal centre (GC) B-cell but the exact stage of B-cell development is unknown. Also, of the 85 KSHV open reading frames that could contribute to viral pathogenesis, the expression of only half has been characterised. It is therefore unclear how KSHV interacts with its host B-cell and how this relates to lymphomagenesis. This thesis concerns the creation and testing of two DNA arrays and their application to the analysis of KSHV and human gene expression in PEL. This study shows that KSHV genes can be divided into five groups based on their expression pattern; class I latent genes, class II latent genes, primary lytic genes, secondary lytic genes and tertiary lytic genes. By analogy with EBV, KSHV latent genes are likely to be necessary for the control of B-cell development and for transformation. Comparison with other B-cell tumour types reveals that PEL has a human gene expression profile similar to plasma cells. This is characterised by low expression of genes involved in proliferation, B-cell signalling, GC B-cell development and NF-κB activation but high expression of genes with functions in the secretory pathway. As is the case for plasma cell tumours, high expression of the vitamin D receptor renders PEL sensitive to growth inhibition by vitamin D analogue drugs. PEL cells also over-express genes involved in inflammation, cell adhesion and invasion, which may be responsible for their presentation in the body cavities. These data suggest that KSHV promotes plasma cell development and that PEL arises as a consequence of this virus-mediated B-cell activation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.398336  DOI: Not available
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