UK-China partnership on Global Food Security: Combating avian tumor diseases for sustainable poultry production

中英全球粮食安全伙伴关系：抗击禽肿瘤疾病以实现可持续家禽生产

基本信息

批准号：
BB/R012865/1
负责人：
YONGXIU YAO
金额：
$ 49.57万
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%2FR012865%2F1
关键词：
UK China partnership Global Food

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). ALV is the most common naturally occurring avian retrovirus that can cause a variety of neoplastic disease conditions in chickens. In addition to causing neoplasia, ALV is known to be associated with reduced productivity and other production problems in affected flocks. Based on the properties of viral envelope glycoproteins, ALV is classified into six subgroups: A, B, C, D, E and J. Originally isolated by the Pirbright Institute in the late 1980s, ALV-J spreads widely and induces myeloid leukosis and a broad spectrum of additional disorders, such as histiocytic sarcoma, hemangiomas and erythroblastosis. The original strains have almost been eradicated from most of the commercial poultry flocks in Europe and the United States but in Asia, the virus evolved into a great variety and recently emerging Chinese isolates coarsely induce various tumours in both commercial laying hen flocks as well as native Chinese breeds of chickens. Defining the molecular background of the tumorigenesisis is needed to develop more effective control and eradication programmes in China. In this proposal, we aim to obtain detailed comprehensive picture on the molecular events to understand and predict the molecular pathways to ALV-J induced cancer. This includes non-coding RNA profiling for the role of non-coding RNAs in ALV-J induced oncogenesis, oncogene myc targetome identification and the role of myc-binding in maintaining the transformed phenotype and myc knockout by CRISPR/Cas9 system for the role of myc in maintaining the transformed phenotype. As the co-infection of ALV-J with other tumor viruses such as Marek's disease virus and Reticuloendotheliosis virus is very common and caused more serious pathogenic effects, we are going to elucidate the synergistic mechanism of ALV-J+REV/ALV-J+MDV co-infection in vitro and in vivo. The findings will be very valuable in developing new approaches for the eradication of ALV-J in China and control of cancers caused by oncogenic viruses. We also want to establish the resistant cell line by editing ALV-J receptor NHE1 using CRISPR/Cas9 system to explore genetic resistant to ALV-J. Finally, we will develop the rapid diagnostic kits to detect ALV-J infection in the field to aid the ALV-J control and eradication in China.

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。 ALV 是最常见的自然存在的禽逆转录病毒，可引起鸡的多种肿瘤性疾病。除了引起肿瘤外，已知 ALV 还与受影响鸡群的生产力下降和其他生产问题有关。根据病毒包膜糖蛋白的特性，ALV 被分为 6 个亚组：A、B、C、D、E 和 J。ALV-J 最初由 Pirbright 研究所于 20 世纪 80 年代末分离出来，广泛传播并诱发骨髓性白血病和广泛的其他疾病，例如组织细胞肉瘤、血管瘤和成红细胞增多症。在欧洲和美国，原始毒株几乎已从大多数商业家禽群中消灭，但在亚洲，该病毒已进化为多种病毒，最近出现的中国分离株可在商业蛋鸡群和本地蛋鸡群中粗略诱发各种肿瘤。中国鸡品种。需要明确肿瘤发生的分子背景，以便在中国制定更有效的控制和根除计划。在本提案中，我们的目标是获得分子事件的详细全面图片，以了解和预测 ALV-J 诱导癌症的分子途径。这包括非编码 RNA 分析，以了解非编码 RNA 在 ALV-J 诱导的肿瘤发生中的作用、致癌基因 myc 靶标组的识别以及 myc 结合在维持转化表型中的作用，以及通过 CRISPR/Cas9 系统进行 myc 敲除的作用myc 维持转化的表型。由于ALV-J与马立克氏病病毒、网状内皮组织增生病毒等其他肿瘤病毒共同感染非常常见，并引起更严重的致病作用，我们将阐明ALV-J+REV/ALV-J+的协同机制MDV 体外和体内双重感染。这些发现对于开发在中国消灭 ALV-J 和控制致癌病毒引起的癌症的新方法非常有价值。我们还想通过CRISPR/Cas9系统编辑ALV-J受体NHE1来建立耐药细胞系，以探索对ALV-J的遗传耐药性。最后，我们将开发现场检测ALV-J感染的快速诊断试剂盒，以帮助中国控制和消灭ALV-J。