Alan Rickinson - Overview

Epstein Barr Virus is linked to a range of human tumours of lymphoid and epithelial origin. Our work (involving Alan Rickinson, Henri-Jacques Delecluse and Andy Bell) focuses principally on three B cell-derived malignancies, Burkitt’s Lymphoma, Hodgkin’s Disease and Post-Transplant Lymphoma, each of which displays a different pattern of virus latent gene expression. We are trying to understand in molecular terms how the virus promoters which drive latent gene transcription are regulated by cellular factors at different stages of B cell differentiation, and in particular how and when the full growth transforming programme is activated and later suppressed in freshly-infected B cells in vivo. This work involves a combination of work in cell culture systems using recombinant viruses with promoter mutations, and the analysis of naturally infected B cell subpopulations in vivo.

A parallel set of studies (involving Alan Rickinson, Steve Lee and Neil Steven) are focused on understanding the immune CD4+ and CD8+ T cell responses which naturally control EBV infection in the immunocompetent host. We are particularly interested in responses which are directed against a subset of virus latent proteins (namely the nuclear antigen EBNA1 and latent membrane proteins 1 and 2) which are potential targets for immunotherapeutic T cells in the context of important malignancies such as Hodgkin’s Disease and the EBV-associated epithelial tumour, nasopharyngeal carcinoma. The two main strands of this work are (i) to understand how these particular proteins are processed for recognition by CD4+ and CD8+ T cells, and (ii) to devise therapeutic vaccination strategies which will induce or boost the relevant responses in tumour patients.