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Investigating the role of Epstein-Barr virus in the pathogenesis of NK and T cell lymphoproliferations

Fox, Christopher Paul (2011)
Ph.D. thesis, University of Birmingham.

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Abstract

Epstein-Barr virus (EBV) is strongly associated with rare but aggressive lymphoproliferative diseases of NK and T cell origin. The finding of clonal and episomal forms of the virus in tumour cells from these clinically diverse diseases indicates involvement of EBV at an early stage of lymphomagenesis. However, many fundamental questions about EBV’s contribution to pathogenesis remain unanswered. In vivo analyses herein found that infection of tonsillar (but not peripheral blood) T cells occasionally occurred in primary and persistent infection, whilst infection of NK cells was a rare event. By contrast, a high EBV load was found in peripheral blood NK cells from 3 adult patients with EBV-associated haemophagocytic-lymphohistiocytosis, a disease previously associated with CD8+ T cell infection in children.

Complementary studies examined EBV latent gene expression in EBV+ T/NK malignancies. Notwithstanding an apparent absence of latent membrane protein 2A and 2B (LMP2A/B), these tumour cells were recognised and killed by LMP2-specific cytotoxic T lymphocytes. This paradox was resolved by identifying a novel LMP2 mRNA, initiated from within the terminal repeat (TR) region of the viral genome and containing downstream epitope-encoding exons. Expression of LMP2-TR in T/NK cell lines and primary tissue implicates this truncated viral protein in T/NK lymphomagenesis.

Type of Work:Ph.D. thesis.
Supervisor(s):Rowe, Martin and Rickinson, Alan
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Cancer Studies
Subjects:RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Institution:University of Birmingham
ID Code:2847
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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