Dissection of the interactions involved in replication of foot and mouth disease virus using RNA aptamers

口蹄疫病毒是最近在英国爆发的一场重大疾病的原因，导致400万头动物被屠宰，经济损失估计接近300亿英镑。它在世界许多地方仍然流行，很明显，这种疾病将在英国进一步爆发。这种疾病是由一种病毒引起的，为了在未来有效地对抗这种感染，我们需要增加对这种疾病因子如何起作用的了解，并找出它与所入侵的细胞的不同之处。病毒由包裹在保护层中的一个或多个核酸片段（DNA或RNA）组成。最简单的外衣是由蛋白质构成的。在感染过程中，病毒将宿主细胞变成生产新病毒颗粒的工厂，然而，只有在病毒核酸在感染细胞中准确复制的情况下，这些新病毒颗粒才能存活。因此，这个过程是病毒生命周期中潜在的“阿喀琉斯之踵”。该项目旨在帮助我们了解口蹄疫病毒的核酸分子是如何通过产生特异性结合这些蛋白质的分子来被复制机制的蛋白质识别的。这些被称为适体的分子可以“模仿”蛋白质的正常结合位点，也可以在其他地方结合。这两种类型的适体都可以影响复制蛋白的作用，帮助我们了解复制过程是如何发生的，并可能确定未来抗病毒药物设计的靶点。

Foot-and-mouth disease virus was the cause of a recent major disease outbreak in the UK that resulted in the slaughter of 4,000,000 animals and financial losses estimated to have approached 30 billion pounds. It remains endemic in many parts of the world and it is clear that further outbreaks of the disease will occur in the UK. The disease is caused by a virus and in order to effectively fight such infections in the future, we need to increase our knowledge of how this disease agent functions and find out what makes it different from the cells it invades. Viruses are composed of one or more pieces of nucleic acid (DNA or RNA) enclosed in a protective coat. The simplest coats are made of protein. During an infection, viruses turn their host's cells into factories for the production of new virus particles, however, these can only be viable if the viral nucleic acid is reproduced accurately in the infected cell. This process is therefore a potential 'Achilles-heel' in the viral life-cycle. This project aims to help us understand how the nucleic acid molecules of foot-and-mouth disease virus are recognised by proteins of the replication machinery by producing molecules that specifically bind to these proteins. These molecules, called aptamers, can either 'mimic' the normal binding sites of the proteins, or can bind elsewhere. Both types of aptamers could affect the action of the replication proteins, helping us understand how the replication process occurs and possibly determine target sites for the design of antiviral drugs in the future.