Understanding RNA packaging signals in foot-and-mouth disease virus (FMDV) for improved vaccine production

口蹄疫病毒(口蹄疫病毒)是一种经济破坏性的牲畜疾病，对发达国家和发展中国家都有影响。世界上最大的挑战之一是满足日益增长的粮食需求。口蹄疫病毒等动物病毒对畜牧业的生产力有重大的负面影响。因此，加强对口蹄疫的控制可以可持续地改善全球畜牧业的业绩，并在世界范围内具有巨大的经济和社会价值，特别是在发展中地区，那里的牲畜被视为使数百万人摆脱贫困的手段。口蹄疫病毒由制造新病毒的“蓝图”组成，包裹在保护性蛋白外壳或衣壳内。蓝图是一个单一的RNA片段，类似于人类的DNA遗传密码。当口蹄疫病毒复制时，它使用RNA蓝图和宿主细胞机制来制造新的蛋白质和新的RNA副本。这些蛋白质组装在一起，形成新的病毒衣壳。RNA是一个单一的线性分子，就像一根长线，但它最终都奇迹般地被包装在衣壳里，形成了一个整齐折叠的球。目前尚不清楚这是如何发生的。我们已经发现，RNA的某些部分可能充当挂钩，帮助RNA抓住病毒蛋白质。这可能会引导RNA折叠成正确的形状，以便被组装的蛋白质包围。这是令人兴奋的，因为人们几十年来一直在想这是如何运作的，现在我们即将找到答案。我们想确定RNA上的钩子是什么，以及它们是如何抓住蛋白质的。这是口蹄疫病毒和许多其他相关病毒生命周期的关键部分。我们相信，我们提出的工作将提供对基因组包装过程的详细新理解，以便我们能够重新编程病毒蓝图，通过提高疫苗的产量和/或稳定性来改善口蹄疫疫苗的生产。

Foot-and-mouth disease virus (FMDV) causes an economically devastating disease of livestock affecting both the developed and developing world. One of the world's biggest challenges is to meet a growing demand for food. Animal viruses such as FMDV have a significant negative impact on productivity of the livestock industries. Thus improved control of FMD could sustainably improve the performance of global livestock industries and have enormous economic and social value worldwide especially in developing regions where livestock are seen as a means to raise millions from poverty. FMDV is composed of a 'blueprint' for making new virus, enclosed within a protective protein shell or capsid. The blueprint is a single piece of RNA, similar to the DNA genetic code in humans. When FMDV replicates, it uses the RNA blueprint and host cell machinery to make new proteins and new copies of the RNA. The proteins assemble together to make new virus capsids. The RNA is a single linear molecule, like a long piece of string but it all ends up miraculously 'packaged' inside the capsid in a neatly folded ball. How this happens is not understood. We have discovered that there are parts of the RNA that might act as hooks to help the RNA grab hold of the virus proteins. This might guide the folding of the RNA into the correct shape for it to be enclosed by the assembling proteins. This is exciting because people have been wondering about how this works for decades and now we are getting close to finding out. We would like to determine what the hooks are on the RNA and how they grab onto the proteins. This is a critical part of the virus life cycle for FMDV and many other related viruses. We believe the work we propose will provide detailed new understanding of the genome packaging process so that we will be able to reprogramme the viral blueprint to improve on the production of FMD vaccines by increasing yield and/or stability of vaccine.