Oncogenic Herpesviruses - Professor Martin Allday

Group leader - Professor Martin Allday

Some human viruses produce persistent or latent infections. This means that after primary infection the host carries the virus (or viral genetic material) for life, generally with no obvious symptoms and in a state of equilibrium with the immune system.

Such long-term, intimate relationships between virus and host can – on rare occasions (often associated with impairment of the immune system) – result in cancer. For example in humans Epstein-Barr virus (EBV) is associated with several B cell lymphomas and carcinomas, Hepatitis B and C viruses are linked to hepatocellular carcinoma and Kaposi’s Sarcoma (KS)-associated virus (KSHV) is involved in the pathogenesis of KS and two B cell lymphomas. In chickens Marek’s disease virus (MDV) is associated with T cell lymphomas. We are interested in the circumstances that lead to the development of virus-associated cancers and specifically the contribution the gamma-herpesvirus EBV makes to the pathogenesis of various B cell lymphomas in humans and how the alpha-herpesvirus MDV induces T cell lymphomas in chickens.

Our current research questions:

• How do the EBNA3 latency-associated proteins of EBV cooperate to regulate cellular gene expression and what role do they play in viral persistence and lymphomagenesis?
• To what extent does latent EBV epigenetically reprogramme B cells in persistence and B cell lymphomagenesis?
• How do EBNA3A and EBNA3C disrupt the regulation of cell cycle checkpoints and contribute to genomic instability in EBV infected B cells?
• Why is the Meq nuclear oncoprotein of MDV essential for T cell lymphomagenesis?
• Can Meq-mutant MDVs act as vaccines for the prevention of Marek’s disease?

Funding and collaborators:

The Wellcome Trust, BBSRC and Leukaemia Research Fund (LRF) fund our research. For the MDV work we have a close collaboration with Dr Venu Nair’s Avian Oncogenic Virus group at the Institute of Animal Health, Compton.

Some of our recent publications:

• Anderton, E., Lee, J. Smith, P., Crook, T., White, R. and Allday M.J., “Two Epstein-Barr virus (EBV) oncoproteins cooperate to repress expression of the pro-apoptotic tumour-suppressor Bim: clues to the pathogenesis of Burkitt’s lymphoma” Oncogene, 17, (2008). 421-33.    
• Young, P, Anderton E., Paschos, K., White R. and Allday, M.J., “Epstein-Barr virus EBNA3A induces the coordinated expression of, and interacts with, a sub-set of chaperones and co-chaperones” J. Gen Virol. 89, (2008). 866-77.
• Thorley-Lawson, D.A. and Allday M.J.,  “The Curious Case of the Tumour virus: 50 years of Burkitt’s Lymphoma.” Nature Reviews Microbiology, 12, (2008). 913-24.
• Paschos, K., Smith, P., Anderton, E., Middeldorp, J.M., White, R.E. and Allday, M.J.,  “Epstein-Barr virus latency in B cells leads to epigenetic repression and CpG-methylation of the tumour suppressor gene Bim” PLoS Pathogens, 5, (2009). e1000492.
• Allday, M.J., “How does EBV complement the activation of Myc in the pathogenesis of Burkitt’s lymphoma?” Seminars in Cancer Biology,  (2009). Epub ahead of print.
• Brown A.C., Smith, L.P., Baigent, S.J. Nair, V. and Allday, M.J., “Homodimerization of the Meq oncoprotein is necessary for the induction of T-cell lymphomas by Marek’s disease virus” J. Virol. (2009). Accepted for publication.