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.

就像在人类中一样，包括鸡在内的许多动物，发展为癌症。但是，与人类不同，鸡的大多数癌症都是由病毒引起的。 Marek病（MD）是一种涉及麻痹和高度恶性T淋巴瘤（白细胞癌）生长的鸡的常见疾病。 MD是由可传播药物Marek病毒（MDV）引起的。 MDV非常具有传染性，对全球Poletry行业构成了重大威胁。估计全球这种疾病的总损失高达20亿英镑。目前，它由疫苗控制，每年使用近220亿次疫苗剂量来控制这种疾病。尽管疫苗广泛，但这种疾病的威胁仍在增加，并且更多的基本研究以了解该病毒引起癌症的机制以制定更有效的控制程序。在英国，诱发鸡的另一种癌症诱发病毒，称为网状内皮症病毒（REV）是癌症的一个很好的模型。使用该病毒研究癌症机制的优点是，可以对从鸟类收集的鸡细胞进行诱导癌症的实验。我们已经使用了该模型，并检查了细胞的分子变化，同时将其转化为癌细胞。我们已经确定了正常癌细胞之间基因表达和小22-核苷酸分子的表达的非常重要的变化，这表明这些变化有助于癌症。在这项新的赠款提案中，将在动物健康研究所（Compton）和ARK-GENOMICS（Roslin Institute）之间共同执行，我们希望扩展这些研究，以获取有关基因表达的详细信息，以使用新的RNA-SEQ技术表达出来，这些信息将在转化过程中提供有关基因表达的详细综合图景。同样，我们还将检查病毒癌蛋白可以直接与DNA结合以改变基因表达以引起癌症的基因组中的序列。我们的目标是使用这种出色的模型系统和Marek的癌症模型来获取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影响癌症的机制非常重要，其中一些病毒对于理解包括人类在内的其他物种的癌症具有价值。最后，该项目的发现对于开发由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

An avian retrovirus uses canonical expression and processing mechanisms to generate viral microRNA.

• DOI: 10.1128/jvi.02921-13
• 发表时间: 2014-01
• 期刊: Journal of virology
• 影响因子: 5.4
• 作者: Yao Y;Smith LP;Nair V;Watson M
• 通讯作者: Watson M

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