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Understanding the function and formation of infectious bronchitis virus membrane rearrangements

了解传染性支气管炎病毒膜重排的功能和形成

基本信息

批准号：
BB/N002350/1
负责人：
Helena Maier
金额：
$ 57.48万
依托单位：
The Pirbright Institute
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FN002350%2F1
关键词：
Understanding function formation infectious bronchitis

项目摘要

Poultry products are a major source of animal protein for human consumption with approximately 55 billion chickens raised globally every year. The UK poultry industry contributes approximately £3.4 billion to the economy annually but infectious diseases, including viruses, are a continual threat to animal welfare and productivity. The infectious disease that results in the largest economic losses to the UK poultry industry is caused by infectious bronchitis virus (IBV). IBV infection results in animal welfare costs and significant economic losses due to poor meat quality, poor egg production and poor egg quality. It is estimated that IBV affects 22 million chickens and costs the UK poultry industry £23 million every year. Currently available vaccines against IBV are costly to produce and do not protect against all of the different circulating viral strains. Therefore, new vaccination strategies are required. By understanding how IBV replicates itself and how it manipulates the host cell to allow replication, it will be possible to develop alternative and potentially more efficient control strategies, benefitting animal welfare, the poultry industry and the UK economy.IBV is a coronavirus with a positive strand RNA (+RNA) genome. A critical step during the life cycle of coronaviruses is RNA synthesis, the process of copying the viral genome for packaging into new virus particles and to allow viral proteins to be produced. IBV RNA synthesis, as for all +RNA viruses, is closely linked with the rearrangement of cellular membranes, providing a platform for the assembly of the viral proteins responsible for RNA synthesis, known as replication-transcription complexes (RTCs), and protecting viral RNA from host defences. However, IBV induces more than one type of rearranged membrane and the role of these different structures in the virus life cycle is not known.This proposal aims to understand the formation of IBV RTCs responsible for viral RNA synthesis. Specifically we will identify where in the cell viral RTCs are located and RNA synthesis takes place. We will also identify which viral and cellular proteins are important for the formation of rearranged membranes. The information gained will not only be useful for understanding how IBV and other coronaviruses replicate but will provide insight into potential ways to alter or prevent virus replication for future vaccine and anti-viral development.

家禽产品是供人类食用的动物蛋白的主要来源，全球每年饲养约550亿只鸡。英国家禽业每年为经济贡献约34亿GB，但包括病毒在内的传染病是对动物福利和生产力的持续威胁。给英国家禽业造成最大经济损失的传染病是由传染性支气管炎病毒(IBV)引起的。IBV感染肉质差、产蛋差、蛋品质差，造成动物福利成本和重大经济损失。据估计，IBV每年影响2200万只鸡，给英国家禽业造成2300万GB的损失。目前可用的IBV疫苗生产成本很高，而且不能预防所有不同的流行病毒株。因此，需要新的疫苗接种策略。通过了解IBV如何自我复制以及它如何操纵宿主细胞进行复制，将有可能开发出替代的、可能更有效的控制策略，从而使动物福利、家禽业和英国经济受益。IBV是一种冠状病毒，具有正链RNA(+RNA)基因组。冠状病毒生命周期中的一个关键步骤是RNA合成，这是复制病毒基因组以包装成新的病毒颗粒并允许产生病毒蛋白的过程。与所有+RNA病毒一样，IBV的RNA合成与细胞膜的重排密切相关，为负责RNA合成的病毒蛋白提供了一个组装平台，称为复制-转录复合体(RTC)，并保护病毒RNA免受宿主防御。然而，IBV可诱导多种类型的膜重排，而这些不同结构在病毒生命周期中的作用尚不清楚。具体地说，我们将确定病毒RTC在细胞中的位置，并进行RNA合成。我们还将确定哪些病毒和细胞蛋白对于重排的膜的形成是重要的。获得的信息不仅有助于了解IBV和其他冠状病毒的复制方式，还将为未来的疫苗和抗病毒开发提供改变或防止病毒复制的潜在方法。