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

马立克氏病（MD）是鸡的一种常见病，包括瘫痪和因高度恶性T淋巴瘤（白细胞癌）的生长而死亡。MD是由一种可传播的病原体马立克氏病病毒（Marek's disease virus， MDV）引起的，这在癌症中并不常见。MDV具有很强的传染性，是全世界家禽业的主要威胁，但可以通过接种疫苗加以控制。为了控制这种疾病，每年使用的疫苗超过50亿剂。然而，病毒的毒力在不断进化，因此需要新的疫苗。病毒获得毒性和产生肿瘤的机制仍然知之甚少。同样，决定有效疫苗毒株的因素仍不清楚。在BBSRC的资助下，我们一直在研究一种名为Meq的蛋白质，这种蛋白质是由癌细胞中的MDV产生的。我们最近的研究结果明确表明，这种蛋白对于MDV诱导肿瘤是绝对必要的（因此它被称为癌蛋白）。此外，已经有可能确定特定的蛋白质：涉及Meq的蛋白质相互作用是其作为癌蛋白功能所必需的。我们已经在meq编码基因中制造了各种明确的突变，产生了减毒（非致病性）MDV，我们证明这些突变可以用作疫苗。这是一项以这项工作为基础的建议，以确定Meq对马立克病的各种病理表现（包括恶性和麻痹形式）的发展的确切贡献，并试图更好地理解什么构成了有效的MDV疫苗株。

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.