Epstein-Barr virus (EBV), a gammaherpes virus widespread in human populations, encodes a set of viral latent genes whose constitutive expression in B cells leads to permanent cell growth. How such growth transforming function is reconciled with the requirement of the virus to persist as an asymptomatic infection in the immunocompetent host remains a challenging question. To date, much of our understanding of this flexibility of EBV's transcriptional programme has come from the studies of three EBV-positive malignancies of B cell origin, Burkitt's lymphoma, Hodgkin's disease and lymphoproliferative disease. However, while the distinct forms of virus latency seen in these tumours are well characterised, their significance to our understanding of the wider biology of EBV, and in particular how B cell differentiation status influences EBV latency, remain unclear.
Our work currently focuses on the following fundamental questions concerning the nature of EBV:B cell interactions in vitro and in vivo:
- Which viral and cellular factors dictate latent promoter choice and thereby determine the form of latent infection ?
- What is the basis of the B lineage specificity of EBV's growth transforming programme ?
- How does EBV colonise and persist within the B cell system in vivo?
- What contribution does EBV make to the pathogenesis of BL, and what is the significance of the different forms of virus latency seen in this tumour?
