Understanding a viral polymerase complex: a multienzyme 'molecular motor' that drives virus replication

了解病毒聚合酶复合物：驱动病毒复制的多酶“分子马达”

• 批准号: BB/F021771/1
• 负责人: Polly Roy
• 金额: $ 67.52万
• 依托单位: London School of Hygiene & Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF021771%2F1
• 关键词: Understanding; viral; polymerase; complex; multienzyme

Viruses can only successfully infect animals by hijacking normal cellular functions and using these to make many more copies of the virus. However, cells do not contain all of the machinery necessary to copy the virus genes, and so the virus has to carry some of this with it when it infects the animal. As this part of the virus has no cellular equivalent, but is necessary for the virus to reproduce, it is a very good target for medicine that interferes with virus infection. Bluetongue virus causes a devastating disease in sheep where up to 70% if infected animals die. For this virus we know all of the genes in the virus, understand the overall structure of the pathogen, and have demonstrated the function of some of the parts of the machinery that copies the virus at a test tube level. What we do not know is precisely how these individual pieces of the machinery work together and that is the focus of this research study. The approach taken will involve a study of the structure of the machinery at a very small scale, as well as experiments that test how well each part of the overall machine is working. Outputs from this research will provide opportunities for the design of new medicine that interferes with the virus machinery and prevents it from copying itself.

病毒只有通过劫持正常的细胞功能并利用这些功能复制更多的病毒才能成功感染动物。然而，细胞并不包含复制病毒基因所需的所有机制，因此病毒在感染动物时必须携带一些病毒基因。由于病毒的这一部分没有细胞等价物，但却是病毒繁殖所必需的，因此它是干扰病毒感染的药物的一个非常好的靶点。蓝舌病病毒在绵羊中引起一种毁灭性的疾病，如果被感染，高达70%的动物死亡。对于这种病毒，我们知道病毒中的所有基因，了解病原体的整体结构，并在试管水平上证明了复制病毒的机器的某些部分的功能。我们所不知道的是这些机器的各个部分是如何协同工作的，这就是这项研究的重点。所采取的方法将涉及在非常小的范围内研究机器的结构，以及测试整个机器的每个部分工作情况的实验。这项研究的成果将为设计新的药物提供机会，这种药物可以干扰病毒机制并防止其自我复制。

项目成果

Bluetongue virus VP1 polymerase activity in vitro: template dependency, dinucleotide priming and cap dependency.

• DOI: 10.1371/journal.pone.0027702
• 发表时间: 2011
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Matsuo E;Roy P
• 通讯作者: Roy P