Recovery of Bluetongue Virus from nucleic acid: configuration optimisation and application

蓝舌病是一种绵羊（有时是牛和山羊）的病毒性疾病，对英国农业构成经济威胁。自1998年以来，蓝舌病的爆发已经在欧洲向北蔓延，去年这种疾病传到了荷兰。BTV的问题显然越来越严重，需要使用现代遗传方法来改进疫苗以及了解复制周期的各个方面。然而，一个重要的瓶颈是无法从序列定义的克隆中恢复BTV。因此，目前不可能改变或删除病毒中的基本基因，以生产减毒株作为候选疫苗。这个项目试图纠正这一点，并为BTV生产一个“反向遗传”系统。去年，研究小组发现了一种从病毒中分离出的病毒遗传物质开始恢复蓝舌病病毒的方法。拟议中的研究建立在这一成功的基础上，以测试完全由克隆基因副本构建病毒的方法，然后故意削弱病毒以制造更好的疫苗。这项研究将专门针对去年在荷兰爆发的病毒株，以制造新的菌株，用于保护英国牲畜免受这种疾病的侵害。如果取得成功，这项研究也有可能应用于制造更好的疫苗，用于治疗导致人类和马疾病的其他病毒。

Bluetongue is a viral disease of sheep (sometimes cattle and goats) that poses an economic threat to UK agriculture. Since 1998, outbreaks of Bluetongue have spread Northwards in Europe and last year the disease reached Holland. The problem of BTV is clearly growing and the use of modern genetic methods to improve vaccines as well as to understand every aspect of the replication cycle is required. A significant bottleneck however, is the inability to recover BTV from sequence defined clones. As a result, the ability to change or delete essential genes in the virus with a view to producing attenuated strains as candidate vaccines is currently impossible. This project seeks to rectify this and produce a 'reverse genetics' system for BTV. Within the last year the research team has discovered a way to recover Bluetongue virus starting from just the viral genetic material isolated from the virus. The proposed research builds on this success to test ways in which the virus can be constructed completely from cloned gene copies and then deliberately weakened to make better vaccines. The research will specifically target the strain of virus that was the cause of last year's outbreak in Holland to make new strains that can be used to protect UK livestock against this disease. If successful it may be possible to also apply the research to make better vaccines for other viruses which cause disease in human and horses.