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

马立克氏病病毒（MDV）Meq癌蛋白在马立克氏病发病机制和MDV疫苗株开发中的作用

• 批准号: BB/G001642/1
• 负责人: Venugopal Nair
• 金额: $ 52.53万
• 依托单位: The Pirbright Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FG001642%2F1
• 关键词: role; Marek; disease; virus; 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.

马立克氏病 (MD) 是鸡的一种常见疾病，导致鸡因高度恶性 T 淋巴瘤（白细胞癌症）生长而导致瘫痪和死亡。 MD 是一种不常见的癌症，它是由马立克氏病病毒 (MDV) 等传染性疾病引起的。 MDV 传染性很强，是全世界家禽业的主要威胁，但可以通过疫苗接种来控制。为了控制这种疾病，每年使用超过 50 亿剂疫苗。然而，病毒不断进化至更强的毒力，因此需要新的疫苗。人们对病毒获得毒力并产生肿瘤的机制仍知之甚少。同样，决定有效疫苗株的因素仍不清楚。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。我们最近的结果明确证明，这种蛋白质对于 MDV 诱导肿瘤绝对是必需的（因此被称为癌蛋白）。此外，还可以鉴定涉及 Meq 的特定蛋白质：蛋白质相互作用，这对于其作为癌蛋白的功能是必需的。我们在 Meq 编码基因中进行了各种确定的突变，产生减毒（非致病性）MDV，我们证明可以将其用作疫苗。这是一项以这项工作为基础的提案，旨在确定 Meq 对马立克氏病各种病理表现（包括恶性和麻痹形式）发展的确切贡献，并尝试更好地了解有效的 MDV 疫苗株的构成。

项目成果

Rate of natural transmission of Marek's disease virus (MDV) to susceptible chickens in the post-challenge period: effect of vaccination with HVT and association with MDV genome count in air.

攻击后马立克氏病病毒 (MDV) 向易感鸡的自然传播率：HVT 疫苗接种的影响以及与空气中 MDV 基因组计数的关联。

• 发表时间: 2010
• 期刊: Zootecnica International
• 作者: Crabb JR

Differential quantification of cloned CVI988 vaccine strain and virulent RB-1B strain of Marek's disease viruses in chicken tissues, using real-time PCR

• DOI: 10.1016/j.rvsc.2010.08.002
• 发表时间: 2011-08-01
• 期刊: RESEARCH IN VETERINARY SCIENCE
• 影响因子: 2.4
• 作者: Baigent, S. J.;Smith, L. P.;Nair, V. K.
• 通讯作者: Nair, V. K.

Induction of lymphomas by inoculation of Marek's disease virus-derived lymphoblastoid cell lines: prevention by CVI988 vaccination.

通过接种马立克氏病病毒衍生的淋巴母细胞系诱导淋巴瘤：通过 CVI988 疫苗接种进行预防。

• DOI: 10.1080/03079457.2012.740159
• 发表时间: 2012
• 期刊: journal of the W.V.P.A
• 作者: Mwangi WN

Analysis of the early immune response to infection by infectious bursal disease virus in chickens differing in their resistance to the disease.

• DOI: 10.1128/jvi.02828-14
• 发表时间: 2015-03
• 期刊: Journal of virology
• 影响因子: 5.4
• 作者: Smith J;Sadeyen JR;Butter C;Kaiser P;Burt DW
• 通讯作者: Burt DW

Epigenetic regulation of the long repeats of Marek's Disease Virus (MDV) associated with latent and lytic expression profiles

马立克氏病病毒（MDV）长重复的表观遗传调控与潜伏和裂解表达谱相关

• 发表时间: 2010
• 期刊: 5th International Workshop on the Molecular Pathogenesis of Marek's Disease Virus, University of Georgia, Athens, USA, 17-20 October 2010
• 作者: Brown A