The application of reverse genetics to the study of pathogenicity in avian pneumovirus

反向遗传学在禽肺病毒致病性研究中的应用

• 批准号: BB/D012171/1
• 负责人: Andrew Easton
• 金额: $ 56.15万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD012171%2F1
• 关键词: application; reverse; genetics; study; pathogenicity

Avian pneumovirus (APV) is a virus causing respiratory disease in birds, particularly in turkeys, resulting in significant losses to poultry farmers as well as suffering to the birds. The virus has eight genes that can cause infected cells to produce nine proteins each of which are then modified in various ways. Some of the proteins are able to make copies of the viral genome (a ribonucleic acid [RNA] molecule that comprises the eight genes with extra pieces at the ends and between them). Other proteins combine with the genome and membranes from the cell to form virus particles that may then infect new cells. The proteins affect the disease caused by the virus both by direct damage to cells and by the reaction of the bird's immune system to them. The immune system helps to clear infections by viruses but also is often responsible for signs of disease as the infected cells are destroyed. The importance of different proteins in the production of disease and also in the production of an effective immune response by weakened viruses used as vaccines is not understood. This is important because the vaccine viruses can become disease producing again. Genetic engineering enables deoxyribonucleic acid (DNA) copies of the virus genome to be copied into virus RNA genomes and eventually into infectious virus. It is possible to make changes in the DNA copies of the virus genome by changing, deleting or inserting nucleotides that are linked together to make up the DNA. These modified DNA copies can then be used to generate viruses and the properties of these viruses studied in cell cultures and turkeys. It provides a means of designing vaccines in a rational manner. The project aims to investigate the importance of various changes observed between different viruses either as a result of mutations or of different modifications of the proteins in different cell types on the tissues in the turkeys where the virus replicates and the disease caused. The importance of changes in vaccine strains for protection will also be studied with the ultimate aim of identifying mutations that will allow virus to be produced that can stimulate a protective immune response but is incapable of causing disease. We already know that deletion of one gene alters the effect of the virus on cells in culture, and in a related virus deletion of a similar gene affects whether the virus grows best in the nose and throat or lungs of various animals. We will study this protein, which has no known function, in more detail. Ultimately, as well as expanding knowledge about the functions of the virus genes in the interaction of the virus with its host information from this study should be useful in designing more effective vaccines benefiting farmers (and turkeys!).

禽肺炎病毒是一种可引致禽鸟呼吸道疾病的病毒，特别是火鸡，不但对家禽饲养者造成重大损失，亦令禽鸟深受其害。这种病毒有八个基因，可以使感染细胞产生九种蛋白质，每种蛋白质都以各种方式进行修饰。一些蛋白质能够复制病毒基因组（一种核糖核酸[RNA]分子，由8个基因组成，在末端和它们之间有额外的片段）。其他蛋白质联合收割机与基因组和细胞膜结合，形成病毒颗粒，然后感染新的细胞。这些蛋白质通过直接损害细胞和鸟类免疫系统对它们的反应来影响病毒引起的疾病。免疫系统有助于清除病毒感染，但也经常负责疾病的迹象，因为受感染的细胞被破坏。不同蛋白质在疾病产生中的重要性以及在作为疫苗使用的弱化病毒产生有效免疫应答中的重要性尚不清楚。这一点很重要，因为疫苗病毒可以再次成为疾病生产者。基因工程使病毒基因组的脱氧核糖核酸（DNA）拷贝能够复制到病毒RNA基因组中，并最终成为传染性病毒。通过改变、删除或插入连接在一起构成DNA的核苷酸，可以改变病毒基因组的DNA拷贝。然后，这些修饰的DNA拷贝可用于产生病毒，并在细胞培养物和火鸡中研究这些病毒的特性。它提供了一种以合理的方式设计疫苗的方法。该项目旨在研究不同病毒之间观察到的各种变化的重要性，这些变化是由于病毒复制和疾病引起的火鸡组织上不同细胞类型中的蛋白质突变或不同修饰造成的。还将研究疫苗株变化对保护的重要性，最终目的是确定允许产生病毒的突变，这些突变可以刺激保护性免疫反应，但不能引起疾病。我们已经知道，一个基因的缺失会改变病毒对培养细胞的影响，而在一个相关的病毒中，一个类似基因的缺失会影响病毒在各种动物的鼻子和喉咙还是肺部生长得最好。我们将更详细地研究这种功能未知的蛋白质。最终，除了扩大有关病毒基因在病毒与其宿主相互作用中的功能的知识外，这项研究的信息应该有助于设计更有效的疫苗，使农民（和火鸡！）受益。