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）是鸡的一种常见疾病，涉及瘫痪，并且通常由于高度恶性T淋巴瘤（白色血细胞的癌症）的生长而死亡。不寻常的癌症，MD是由一种可传播的媒介，马立克氏病病毒（MDV）。MDV具有很强的传染性，是全球家禽业的主要威胁，但可以通过接种疫苗加以控制。每年有超过50亿剂疫苗用于控制这种疾病。然而，病毒不断进化，毒力越来越强，因此需要新的疫苗。对该病毒获得毒力和产生肿瘤的机制仍然知之甚少。同样，决定有效疫苗株的因素仍然不清楚。在BBSRC的财政支持下，我们一直在研究一种名为Meq的蛋白质，它是由MDV在癌细胞中产生的。我们最近的研究结果已经明确表明，这种蛋白质对于MDV诱导肿瘤是绝对必要的（因此它被称为癌蛋白）。此外，它已经有可能确定特定的蛋白质：蛋白质相互作用涉及Meq是必要的，其功能作为一个癌蛋白。我们已经在Meq编码基因中进行了各种确定的突变，这些突变产生了减毒（非致病性）MDV，我们表明这些MDV可以用作疫苗。这是一个建议，以建立这项工作，以确定确切的贡献，Meq使马立克氏病的发展，在其各种病理表现/包括恶性和麻痹形式/并试图更好地了解什么是一个有效的疫苗株的MDV。

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.