Use of synchrotron radiation to investigate the structure of genomic RNAs inside viral capsids

使用同步辐射研究病毒衣壳内基因组 RNA 的结构

• 批准号: BB/I002456/1
• 负责人: Peter Stockley
• 金额: $ 7.4万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI002456%2F1
• 关键词: Use; synchrotron; radiation; investigate; structure

The simplest viruses consist only of nucleic acids surrounded by a protective shell of protein molecules. We are studying the structures, assembly and disassembly of viruses in which the nucleic acid component is a single-stranded (ss) RNA. ssRNA viruses encompass broad classes of infectious agents including those responsible for the common cold, some cancers and AIDS. The most successful line of defence against any virus is vaccination with an appropriate immunogen but in many cases this has proved to be very difficult or impossible. We believe that the improved understanding of the roles of the ssRNA in the assembly and disassembly of such viruses resulting from the work we have recently carried out gives us unique insights that will open up novel therapeutic targets, potentially allowing the efficiency of progeny virus assembly to be reduced dramatically so that non-infectious, partially assembled particles can prime the host's immune system, leading to viral clearance. Central to this effort is an understanding of teh structure(s) of the ssRNA within the viral particle. We are therefore proposing to test whether the main technique available for interogating such structures, X-ray footprinting, can be used on our test viruses. This work involves use of the new Diamond Synchrotron in Oxfordshire where we will build an instrument to allow viruses to be exposed to X-rays in a defined way. The resulting modified and harmless ssRNAs will then be examined in Leeds and by our US collaborators in Oklahoma.

最简单的病毒只由被蛋白质分子保护壳包围的核酸组成。我们正在研究病毒的结构，组装和拆卸，其中核酸成分是单链（ss）RNA。ssRNA病毒涵盖广泛类别的传染因子，包括导致普通感冒、某些癌症和艾滋病的那些。针对任何病毒的最成功的防线是接种适当的免疫原，但在许多情况下，这已被证明是非常困难或不可能的。我们相信，通过我们最近开展的工作，对ssRNA在此类病毒组装和拆卸中的作用有了更好的理解，这为我们提供了独特的见解，这将开辟新的治疗靶点，可能使子代病毒组装的效率大幅降低，从而使非感染性的部分组装颗粒可以启动宿主的免疫系统，导致病毒清除。这项工作的核心是理解病毒颗粒内ssRNA的结构。因此，我们建议测试可用于询问此类结构的主要技术，X射线足迹法，是否可用于我们的测试病毒。这项工作涉及使用牛津郡的新钻石同步加速器，我们将在那里建造一种仪器，使病毒以确定的方式暴露于X射线。然后将在利兹和我们的美国合作者在俄克拉荷马州对所产生的修饰和无害的ssRNA进行检查。