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

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、组装和拆解，其中核酸成分是单链(Ss)RNA。单链RNA病毒包括广泛类别的感染性病原体，包括导致普通感冒、一些癌症和艾滋病的病原体。对任何病毒最成功的防线是接种适当的免疫原，但在许多情况下，这被证明是非常困难或不可能的。我们相信，由于我们最近开展的工作，对单链RNA在此类病毒组装和分解中作用的了解有所提高，这给了我们独特的见解，将打开新的治疗靶点，潜在地使子代病毒组装的效率大大降低，从而使非传染性的、部分组装的颗粒能够启动宿主的免疫系统，导致病毒清除。这项工作的核心是了解病毒颗粒内单链RNA的结构(S)。因此，我们建议测试可用于检测这种结构的主要技术--X射线足迹技术是否可以用于我们的测试病毒。这项工作包括在牛津郡使用新的钻石同步加速器，在那里我们将建造一台仪器，允许病毒以特定的方式暴露在X射线下。随后，利兹和我们在俄克拉何马州的美国合作者将对修改后的无害单链RNA进行检查。

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.