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

解开谜团：分段双链RNA病毒如何包装其基因组

• 批准号: BB/P00542X/1
• 负责人: Polly Roy
• 金额: $ 81.66万
• 依托单位: London School of Hygiene & Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FP00542X%2F1
• 关键词: Unravelling; tangle; how; segmented; double

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.

病毒是专性寄生虫，病毒基因组是维持病毒存活的最重要组成部分。一旦病毒感染宿主细胞（人、动物、植物或鱼），它们必须复制，即复制其成分并组装成可存活的子代病毒，以便传播。这种病毒合成过程只有在病毒基因组以正确的形式被整合到新的子代中才有可能。如果基因组是多片段的，病毒就特别难以整合基因组，而许多病毒（例如流感病毒）往往就是这种情况。了解这些携带不同信息的多个基因片段如何以正确的顺序和形式组合在一起，对于了解病毒如何繁殖和传播至关重要。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，本项目将重点研究动物病毒，特别是羊蓝舌病病毒（BTV），其主要特点是其10个基因片段不是DNA，而是RNA分子或片段，每个代表一个基因，每个产生特定的病毒蛋白。我们处于这一研究领域的前沿。在之前BBSRC资助的项目中，我们已经开发了独特的工具、技术、试剂和一系列新的分析系统，这些系统已经确定了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。选择和包装的精确性质，即获得十个片段中的每一个片段的一个副本，而不是一个片段的多个副本，是一个复杂和高度调控的过程，因为病毒必须区分细胞和病毒基因。我们将利用我们的工具和分析方法，以及一些最近才由其他科学家开发的尖端方法。我们将定义这一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，将我们自己的方法和专业知识与其他生物和物理科学相结合。在对有关病原体进行基础研究的基础上，长期改善动物福利是很重要的。BTV在某些家畜中具有高致病性，最近在英国和欧洲出现。了解病毒基因组生命周期中这些至关重要的基本过程，将有可能开发出针对蓝舌病和其他影响牲畜的病毒性疾病的新型、更安全的设计疫苗。这些数据还将有助于开发新的干预措施，以改善未来的疾病管理。

项目成果

Rotavirus Genomic RNA Complex Forms via Specific RNA-RNA Interactions: Disruption of RNA Complex Inhibits Virus Infectivity.

• DOI: 10.3390/v9070167
• 发表时间: 2017-06-29
• 期刊: Viruses
• 作者: Fajardo T;Sung PY;Celma CC;Roy P
• 通讯作者: Roy P

Bluetongue virus assembly and exit pathways.

• DOI: 10.1016/bs.aivir.2020.08.002
• 发表时间: 2020
• 期刊: Advances in virus research
• 作者: Roy P

RNA Origami: Packaging a Segmented Genome in Orbivirus Assembly and Replication.

• DOI: 10.3390/v13091841
• 发表时间: 2021-09-15
• 期刊: Viruses
• 作者: Sung PY;Roy P
• 通讯作者: Roy P

Interaction between a Unique Minor Protein and a Major Capsid Protein of Bluetongue Virus Controls Virus Infectivity.

独特的小蛋白质与蓝肠病毒的主要衣壳蛋白之间的相互作用可控制病毒感染性。

• DOI: 10.1128/jvi.01784-17
• 发表时间: 2018-02-01
• 期刊: Journal of virology
• 影响因子: 5.4
• 作者: Matsuo E;Yamazaki K;Tsuruta H;Roy P
• 通讯作者: Roy P

Dynamic network approach for the modelling of genomic sub-complexes in multi-segmented viruses.

• DOI: 10.1093/nar/gky881
• 发表时间: 2018-12-14
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: AlShaikhahmed K;Leonov G;Sung PY;Bingham RJ;Twarock R;Roy P
• 通讯作者: Roy P