By chance or design: Defining the genome packaging signals for a multi-segmented RNA virus

偶然还是有意为之：定义多片段 RNA 病毒的基因组包装信号

• 批准号: BB/J014877/1
• 负责人: Polly Roy
• 金额: $ 77.08万
• 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: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FJ014877%2F1
• 关键词: chance; design; Defining; genome; packaging

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 or plant) they must replicate their genome and multiply in order for them 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 they are 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's main aim is to understand how these multiple pieces are incorporated and dissecting the exact manner and signals involved in the process. The project will focus on animal viruses, particularly Bluetongue virus (BTV) of sheep as well as other related viruses (African horse sickness virus and Epizootic haemorrhagic disease of deer virus). BTV is primarily characterized by its genome of 10 pieces of RNA, each representing single gene and each generating specific viral proteins. We are exceptionally positioned at the forefront of this field of research and our laboratory has developed unique tools, techniques and reagents over the years that are tailored for researching these viruses. Recently we have pioneered two key technologies for BTV, a cell-free reconstitution (assembly) of infectious virus system and a reverse genetics system that make infectious virus "wholly" from synthetic genes. 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 work may have direct effect on animal wellbeing as well as economic consequences.

病毒是专性寄生虫，病毒基因组是保持病毒存活的最重要组成部分。一旦病毒感染宿主细胞（人类、动物或植物），它们必须复制其基因组并繁殖，以便传播。只有当病毒基因组以正确的形式整合到新的子代中时，这种病毒合成过程才是可能的。如果病毒是多个片段，则它们特别难以并入基因组，这在许多病毒（例如流感病毒）中经常是这种情况。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整合，对于了解病毒如何繁殖和传播至关重要。这些信息的缺乏已经在多年来对许多病毒的研究和理解中形成了瓶颈。因此，本项目的主要目的是了解这些多个部分是如何合并的，并剖析该过程中涉及的确切方式和信号。该项目将侧重于动物病毒，特别是羊蓝舌病病毒以及其他相关病毒（非洲马瘟病毒和鹿流行性出血病病毒）。BTV的主要特征是其基因组由10段RNA组成，每段RNA代表单个基因，每段RNA产生特定的病毒蛋白。我们处于这一研究领域的最前沿，我们的实验室多年来开发了独特的工具、技术和试剂，专门用于研究这些病毒。最近，我们开创了BTV的两项关键技术，即感染性病毒的无细胞重组（组装）系统和使感染性病毒“完全”来自合成基因的反向遗传学系统。BTV在某些牲畜中具有高致病性，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，可能是影响牲畜的其他病毒性疾病。这项工作可能会对动物的健康和经济后果产生直接影响。

项目成果

Structural constraints in the packaging of bluetongue virus genomic segments.

蓝肠病毒基因组段包装中的结构约束。

• DOI: 10.1099/vir.0.066647-0
• 发表时间: 2014-10
• 期刊: The Journal of general virology
• 作者: Burkhardt C;Sung PY;Celma CC;Roy P
• 通讯作者: Roy P

Structure based modification of Bluetongue virus helicase protein VP6 to produce a viable VP6-truncated BTV.

• DOI: 10.1016/j.bbrc.2014.08.028
• 发表时间: 2014-09-05
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Matsuo, Eiko;Leon, Esther;Matthews, Steve J.;Roy, Polly
• 通讯作者: Roy, Polly

Low-pH structures of bluetongue virus inform non-enveloped virus cell entry

蓝舌病毒的低 pH 结构有助于非包膜病毒进入细胞

• 期刊: Nature Microbiology
• 影响因子: 28.3
• 作者: X Xia

Disruption of Specific RNA-RNA Interactions in a Double-Stranded RNA Virus Inhibits Genome Packaging and Virus Infectivity.

• DOI: 10.1371/journal.ppat.1005321
• 发表时间: 2015-12
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Fajardo T Jr;Sung PY;Roy P
• 通讯作者: Roy P

Generation of infectious RNA complexes in Orbiviruses: RNA-RNA interactions of genomic segments.

• DOI: 10.18632/oncotarget.12496
• 发表时间: 2016-11-08
• 期刊: Oncotarget
• 作者: Fajardo T Jr;AlShaikhahmed K;Roy P
• 通讯作者: Roy P