Unravelling a tangle: how segmented double-stranded RNA viruses package their genome

病毒是专性寄生虫，而病毒基因组是维持病毒存活的最重要的组成部分。一旦病毒感染宿主细胞(人、动物、植物或鱼类)，它们就必须复制，即复制其组成部分并组装成可存活的后代病毒以进行传播。只有当病毒基因组以正确的形式整合到新的后代中时，这种病毒合成过程才是可能的。对于病毒来说，如果基因组是多个片段的话就特别困难，许多病毒(例如流感病毒)通常都是这种情况。了解这些携带不同信息的多个基因片段是如何以正确的顺序和形式结合在一起的，对于了解病毒如何繁殖和传播是至关重要的。这些信息的缺乏造成了多年来对许多病毒的研究和理解的瓶颈。因此，该项目将专注于动物病毒，特别是绵羊蓝舌病毒(BTV)，其主要特征是其10个基因片段不是DNA，而是RNA分子或片段，每个基因代表一个基因，每个基因产生特定的病毒蛋白。我们处于这一研究领域的前沿。在BBSRC以前资助的项目中，我们开发了独特的工具、技术、试剂和一系列新颖的检测系统，这些系统已经定义了BTV如何招募它们的片段并组装成具有传播能力的活病毒的一些基本步骤。选择和包装的确切性质，即获得10个片段中每一个的单一拷贝，而不是一个片段的多个拷贝，是一个复杂和高度监管的过程，因为病毒必须区分细胞基因和病毒基因。我们将利用我们的工具和化验，以及其他科学家最近才开发的一些尖端方法。我们将定义这个定义不明确的复杂过程，以提供有关BTV和相关病毒如何包装其基因的信息，并通过与专家合作，结合其他生物和物理科学，利用我们自己的方法和专业知识。通过对相关病原体的基础研究，长期改善动物福利是重要的。BTV在某些牲畜中具有高度致病性，最近在英国和欧洲出现。了解病毒基因组生命周期中的这些至关重要的基本过程将使开发新的、更安全的蓝舌病疫苗成为可能，蓝舌病可能是影响牲畜的其他病毒疾病。这些数据还将允许开发新的干预措施，以改善未来的疾病管理。

Viruses are obligate parasites and the viral genome is the most important component in keeping a virus alive. Once viruses infect a host cell (human, animal, plant or fish) they must replicate, i.e. make copies of their components and assemble into viable progeny viruses in order to spread. This process of virus synthesis is only possible if the viral genome is incorporated into the new progeny in the correct form. It is particularly difficult for viruses to incorporate the genome if it is in multiple pieces, which is often the case in many viruses (e.g. influenza virus). Understanding how these multiple pieces of genes, each carrying different messages, are incorporated in the correct order and form is essential to understanding how viruses multiply and spread. The lack of this information has created a bottleneck in the research and understanding of many viruses over the years. Therefore this project will focus on animal viruses, particularly Bluetongue virus (BTV) of sheep, which is primarily characterized by its 10 pieces of genes that are not DNA but RNA molecules or segments, each representing a single gene and each generating specific viral proteins. We are exceptionally positioned at the forefront of this field of research. In previous BBSRC funded projects, we have developed unique tools, techniques, reagents and a series of novel assay systems that have already defined some of the essential steps of how BTV may recruit their segments and assemble into a viable virus, competent for spreading. The precise nature of selection and packaging, that is acquiring a single copy of each of ten segments rather than multiple copies of one, is a complex and highly regulated process as the virus must differentiate between cellular and viral genes. We will take advantages of our tools and assays as well as some of the cutting-edge methods that have been developed only recently by other scientists. We will define this poorly-defined complex process to provide information on how BTV and related viruses package their genes and utilise our own methods and expertise in combination with the other biological and physical sciences through collaboration with experts.Long term improvements in animal welfare underpinned by basic research into the pathogen concerned are important. BTV is highly pathogenic in certain livestock and has recently emerged in the UK and Europe. Understanding these vital basic processes in the life cycle of the viral genome will make it possible to develop novel, safer designer vaccines for Bluetongue disease and may be other viral diseases that affect livestock. The data will also allow for the development of novel interventions to improve future disease management.