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

了解口蹄疫病毒 (FMDV) 中的 RNA 包装信号以改进疫苗生产

基本信息

批准号：
BB/V008323/1
负责人：
Tobias Tuthill
金额：
$ 54.62万
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：
2021
资助国家：
英国
起止时间：
2021 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FV008323%2F1
关键词：
Understanding RNA packaging signals foot

项目摘要

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.

口蹄疫病毒（FMDV）是一种经济上毁灭性的牲畜疾病，影响到发达国家和发展中国家。世界面临的最大挑战之一是满足日益增长的粮食需求。动物病毒如口蹄疫病毒对畜牧业的生产力具有显著的负面影响。因此，改善口蹄疫的控制可以可持续地改善全球畜牧业的表现，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，畜牧业被视为使数百万人脱贫的手段。口蹄疫病毒是由一个“蓝图”，使新的病毒，封闭在一个保护性的蛋白质外壳或衣壳。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RNA的新拷贝。这些蛋白质聚集在一起形成新的病毒衣壳。RNA是一个单一的线性分子，就像一根长长的绳子，但它最终奇迹般地“包装”在衣壳内，形成一个整齐折叠的球。这是如何发生的还不清楚。我们已经发现，RNA的某些部分可能起到钩子的作用，帮助RNA抓住病毒蛋白。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想知道这是如何工作的，现在我们即将找到答案。我们想确定RNA上的钩子是什么，以及它们如何抓住蛋白质。这是口蹄疫病毒和许多其他相关病毒的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的新理解，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。