Understanding the function and formation of infectious bronchitis virus membrane rearrangements

家禽产品是人类消费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34亿英镑，但包括病毒在内的传染病对动物福利和生产力构成持续威胁。对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感染导致动物福利成本和显著的经济损失，这是由于肉品质差、产蛋量差和蛋品质差。据估计，IBV影响2200万只鸡，每年给英国家禽业造成2300万英镑的损失。目前可用的针对IBV的疫苗生产成本高，并且不能保护所有不同的循环病毒株。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以允许复制，将有可能开发替代的和潜在的更有效的控制策略，从而使动物福利，家禽业和英国经济受益。IBV是一种具有正链RNA（+RNA）基因组的冠状病毒。冠状病毒生命周期中的一个关键步骤是RNA合成，即复制病毒基因组以包装成新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 RNA合成与细胞膜的重排密切相关，为负责RNA合成的病毒蛋白质（称为复制-转录复合物（RTC））的组装提供平台，并保护病毒RNA免受宿主防御。然而，IBV诱导一种以上类型的重排膜和这些不同的结构在病毒的生命周期中的作用是未知的。本提案旨在了解负责病毒RNA合成的IBV RTC的形成。具体来说，我们将确定病毒RTCs位于细胞中的何处，并进行RNA合成。我们还将确定哪些病毒和细胞蛋白质对重排膜的形成是重要的。所获得的信息不仅有助于了解IBV和其他冠状病毒如何复制，还将为未来疫苗和抗病毒开发提供改变或预防病毒复制的潜在方法。

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.