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

剖析 MDV 癌蛋白 Meq 的分子通路，以了解发病机制并帮助疫苗开发

基本信息

批准号：
BB/R007896/1
负责人：
YONGXIU YAO
金额：
$ 57.03万
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：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FR007896%2F1
关键词：
Dissecting molecular pathways MDV oncoprotein

项目摘要

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.

传染病给家禽养殖的各个环节带来直接和间接的损失，其中由病毒引起的肿瘤性疾病是全世界家禽业面临的主要经济问题。引起鸡肿瘤感染的致癌病毒是由马立克氏病病毒(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 是由传染性病毒 MDV 引起的。 MDV 传染性很强，是全球家禽业的主要威胁。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，该病是通过疫苗接种来控制的，每年使用近220亿剂疫苗来控制该疾病。尽管疫苗接种广泛，但由于MDV毒力不断进化，这种疾病的威胁仍在增加，需要进行更多基础研究来了解这种病毒导致癌症的机制，以制定更有效的控制计划。 Meq 是 MDV 诱导的肿瘤发生中的主要癌蛋白。此前，我们已经确定了癌细胞中的 Meq 靶标组。在这项由 Pirbright 研究所和 Roslin 研究所联合开展的新资助提案中，我们希望扩展这些研究，以使用包括 CRISPR/我们最近在实验室建立了 Cas9 基因组编辑和内源蛋白快速免疫沉淀质谱 (RIME)，用于 Meq 相互作用组鉴定。这项研究对于了解这种病毒诱发癌症的机制非常重要，其中一些机制对于了解包括人类在内的其他物种的癌症也很有价值。最后，该项目的研究结果对于开发控制致癌病毒引起的癌症的新方法非常有价值。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Patterns of RNA Editing in Newcastle Disease Virus Infections.

DOI：
10.3390/v12111249
发表时间：
2020-11-02
期刊：
Viruses
影响因子：
0
作者：
Jadhav A;Zhao L;Ledda A;Liu W;Ding C;Nair V;Ferretti L
通讯作者：
Ferretti L

Simultaneous Protective Immune Responses of Ducks against Duck Plague and Fowl Cholera by Recombinant Duck Enteritis Virus Vector Expressing Pasteurella multocida OmpH Gene.

DOI：
10.3390/vaccines10081358
发表时间：
2022-08-19
期刊：
VACCINES
影响因子：
7.8
作者：
Apinda, Nisachon;Muenthaisong, Anucha;Chomjit, Paweena;Sangkakam, Kanokwan;Nambooppha, Boondarika;Rittipornlertrak, Amarin;Koonyosying, Pongpisid;Yao, Yongxiu;Nair, Venugopal;Sthitmatee, Nattawooti
通讯作者：
Sthitmatee, Nattawooti

Genomic Diversity and Evolution of Quasispecies in Newcastle Disease Virus Infections.