Defining the cistrome and quantitative transcriptome of virus-transformed cells using massively parallel sequencing

使用大规模并行测序定义病毒转化细胞的顺反组和定量转录组

• 批准号: BB/I014284/1
• 负责人: Venugopal Nair
• 金额: $ 56.39万
• 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: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI014284%2F1
• 关键词: Defining; cistrome; quantitative; transcriptome; virus

As in humans, many animals including chickens, develop cancer. However, unlike in humans, most of the cancers in chickens are caused by viruses. 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, Marek's disease virus (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 the increase, and more fundamental studies to understand the mechanisms by which this virus cause cancer is needed to develop more effective control programmes. Another cancer inducing virus of chickens less common in the UK called Reticuloendotheliosis virus (REV) is a very good model for cancer. The advantage of using this virus for studying the mechanisms of cancer is that the experiments to induce cancer can be done on chicken cells collected from birds. We have used this model and examined the molecular changes to the cells while it is transformed into cancer cells. We have identified very important changes in the expression of genes and small 22-nucleotide microRNAs molecules between normal cancer cells, suggesting that these changes contribute to cancer. In this new grant proposal, to be carried out jointly between the Institute for Animal Health (Compton) and ARK-Genomics (Roslin Institute), we want to extend these studies to obtain detailed information on the changes in the expression of genes using the new RNA-Seq technology that will provide a much detailed comprehensive picture on the expression of genes during the transformation process. Similarly, we will also examine the sequences in the genomes where viral oncoproteins can directly bind to the DNA to change the gene expression to cause cancer. We aim to use this excellent model system and Marek's disease cancer model to obtain detailed gene expression data to understand and predict the molecular pathways to cancer. The study is very important to understand the mechanisms by which these viruses induce 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.

与人类一样，包括鸡在内的许多动物都会患癌症。然而，与人类不同的是，鸡的大多数癌症是由病毒引起的。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 是由马立克氏病病毒 (MDV) 等传染媒介引起的。 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 亿英镑。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。另一种在英国不太常见的鸡诱发癌症病毒，称为网状内皮增生病毒（REV），是一种非常好的癌症模型。使用这种病毒研究癌症机制的优点是可以在从鸟类身上收集的鸡细胞上进行诱发癌症的实验。我们使用这个模型并检查了细胞转化为癌细胞时的分子变化。我们已经发现正常癌细胞之间基因和小 22 核苷酸 microRNA 分子表达的非常重要的变化，表明这些变化有助于癌症。在动物健康研究所（康普顿）和 ARK-Genomics（罗斯林研究所）联合开展的这项新资助提案中，我们希望扩展这些研究，利用新的 RNA-Seq 技术获得基因表达变化的详细信息，该技术将提供转化过程中基因表达的更详细的全面信息。同样，我们还将检查基因组中的序列，在这些序列中，病毒癌蛋白可以直接与 DNA 结合，从而改变基因表达从而导致癌症。我们的目标是利用这个优秀的模型系统和马立克氏病癌症模型来获得详细的基因表达数据，以了解和预测癌症的分子途径。这项研究对于了解这些病毒诱发癌症的机制非常重要，其中一些对于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

Novel microRNAs encoded by duck enteritis virus.

• DOI: 10.1099/vir.0.040634-0
• 发表时间: 2012-07
• 期刊: The Journal of general virology
• 作者: Yongxiu Yao;Lorraine P. Smith;L. Petherbridge;M. Watson;V. Nair

Activation of gga-miR-155 by reticuloendotheliosis virus T strain and its contribution to transformation.

• DOI: 10.1099/jgv.0.000718
• 发表时间: 2017-04
• 期刊: The Journal of general virology
• 作者: Yao Y;Vasoya D;Kgosana L;Smith LP;Gao Y;Wang X;Watson M;Nair V
• 通讯作者: Nair V

Differentially expressed genes during spontaneous lytic switch of Marek's disease virus in lymphoblastoid cell lines determined by global gene expression profiling.

• DOI: 10.1099/jgv.0.000744
• 发表时间: 2017-04
• 期刊: The Journal of general virology
• 作者: Mwangi WN;Vasoya D;Kgosana LB;Watson M;Nair V
• 通讯作者: Nair V

MicroRNA expression profiles in avian haemopoietic cells.

• DOI: 10.3389/fgene.2013.00153
• 发表时间: 2013
• 期刊: Frontiers in genetics
• 影响因子: 3.7
• 作者: Yao Y;Charlesworth J;Nair V;Watson M
• 通讯作者: Watson M

Role of virus-encoded microRNAs in Avian viral diseases.

• DOI: 10.3390/v6031379
• 发表时间: 2014-03-21
• 期刊: Viruses
• 作者: Yao Y;Nair V
• 通讯作者: Nair V