Mechanisms of Epstein-Barr virus lymphomagenesis


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Martin Rowe1
1University of Birmingham, Birmingham, UK

Abstract

Epstein-Barr virus (EBV) was first discovered in 1964 in the tumour cells from a patient with Burkitt’s lymphoma. This momentous observation led to EBV being the first human virus to be implicated in the development of a human cancer. Subsequently, EBV has been associated with at least 10 different types of tumours, the best studied being the B cell tumours, Burkitt’s lymphoma, Hodgkins lymphoma, and the lymphomas to which immunosuppressed post-transplant patients are predisposed; and the epithelial cell tumour, undifferentiated nasopharyngeal carcinoma.

EBV has the remarkable property of being able to growth-transform primary resting B cells in vitro into lymphoblastoid cell lines, which has provided a convenient experimental model for investigating the mechanisms of EBV-induced cellular transformation. A large body of work from several laboratories, including our own, has elucidated many of the key mechanisms of EBV-induced cancers, particularly the lymphomas. Interestingly, many of the key advances have arisen from attempts to better understand how EBV establishes largely asymptomatic persistence in healthy immunocompetent individuals.

More recently, we have turned our attention to studying the poorly understood EBV-associated tumours of NK cell or T cell origin. Whilst quite rare, these tumours are clinically important, being clinically aggressive and difficult to treat and having dismal prognosis. This area of research has been largely neglected, partly because of the rarity of the tumours and partly because infection of these cell-types does not conveniently fit into current dogma of the normal biology of EBV persistence. In this presentation recent progress in this area will be outlined.