Dissecting the molecular pathways of MDV oncoprotein Meq for understanding pathogenesis and aid vaccine development

传染病在家禽养殖的各个环节造成直接和间接的损失，其中由病毒引起的肿瘤疾病是世界范围内家禽业面临的一个主要经济问题。引起鸡肿瘤感染的致癌病毒是由马立克病病毒（MDV）组成的疱疹病毒和由网状内皮增生病毒（REV）和禽白血病病毒（ALV）组成的逆转录病毒。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是由传染性病原体MDV引起的。MDV具有很强的传染性，是全世界家禽业的主要威胁。据估计，全世界因这种疾病造成的总损失高达20亿美元。目前，它是通过接种疫苗来控制的，为了控制这种疾病，每年使用近220亿剂疫苗。尽管广泛接种疫苗，但由于MDV不断向更大的毒性演变，该病的威胁正在增加，需要进行更基础的研究，以了解该病毒导致癌症的机制，以制定更有效的控制规划。Meq是MDV诱导肿瘤发生的主要癌蛋白。此前，我们已经在癌细胞中发现了Meq靶组。在这项由Pirbright研究所和Roslin研究所联合开展的新拨款申请中，我们希望扩展这些研究，以使用一些先进的方法，包括我们最近在实验室建立的CRISPR/Cas9基因组编辑和内源性蛋白（RIME）快速免疫沉淀质谱法（用于Meq相互作用组鉴定），获得Meq及其靶点在MDV诱导的肿瘤发生中的作用的详细信息。这项研究对了解这种病毒诱发癌症的机制非常重要，其中一些对了解包括人类在内的其他物种的癌症很有价值。最后，该项目的研究结果将在开发控制由致瘤病毒引起的癌症的新方法方面非常有价值。

Infectious diseases result in direct and indirect losses at various steps of poultry farming and amongst them neoplastic disease caused by viruses is a major economic problem faced by the poultry industry worldwide. The oncogenic viruses causing neoplastic infection in chickens are herpesviruses comprising of Marek's disease virus (MDV) and retroviruses comprising of reticuloendotheliosis virus (REV) and avian leucosis virus (ALV). 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). MD is caused by a transmissible agent MDV. MDV is very contagious and is a major threat to the poultry industry worldwide. The estimated total loss from this disease worldwide is up to $2 billion. Presently, it is controlled by vaccination, and nearly 22 billion vaccine doses a year are used in an attempt to control the disease. Despite widespread vaccination, the threat from this disease is on increase due to continued evolution of MDV towards greater virulence, and more fundamental studies to understand the mechanisms by which this virus causes cancer is needed to develop more effective control programmes. Meq is the major oncoprotein in MDV induced tumorigenesis. Previously, we have identified Meq targetome in cancer cells. In this new grant proposal, to be carried out jointly between the Pirbright Institute and Roslin Institute, we want to extend these studies to obtain detailed information on the role of Meq and its targets in MDV induced oncogenesis using a number of advanced approaches including CRISPR/Cas9 genome editing we have recently established in the lab and rapid immunoprecipitation mass spectrometry of endogenous proteins (RIME) for Meq interactome identification. The study is very important to understand the mechanisms by which this virus induces cancer, some of which are valuable in understanding cancer in other species including humans. Finally, the findings from the project will be very valuable in developing new approaches for the control of cancers caused by oncogenic viruses.