Marek's disease virus (MDV) Meq oncoprotein in the pathogenesis of Marek's disease and the development of MDV vaccine strains

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Marek's disease (MD) is a common disease of chickens involving paralysis and commonly death from the growth of highly malignant T lymphomas (cancers of white blood cells). Unusual for a cancer, MD is caused by a transmissible agent, Marek's disease virus (MDV). MDV is very contagious and is a major threat to the poultry industry worldwide, but it can be controlled by vaccination. More than 5 billion vaccine doses a year are used in an attempt to control the disease. However, there is a continuous evolution of the virus towards greater virulence and consequently new vaccines are required. The mechanisms by which the virus gains virulence and produces tumours remain very poorly understood. Similarly, the factors that determine an effective vaccine strain remain unclear. With financial support from the BBSRC, we have been studying a protein called Meq that is made by MDV in the cancer cells. Our recent results have demonstrated unequivocally that this protein is absolutely essential for the induction of tumours by MDV (it is therefore known as an oncoprotein). Moreover it has been possible to identify specific protein:protein interactions involving Meq that are necessary for its function as an oncoprotein. We have made various defined mutations in the Meq-encoding gene that produce attenuated (non-pathogenic) MDV that we showed can be used as vaccines. This is a proposal to build on this work in order to determine the precise contribution that Meq makes to the development of Marek's disease in its various pathological manifestations / including malignant and paralytic forms / and to try and understand better what constitutes an effective vaccine strain of MDV.