Cellular immunity to herpesvirus infections: studies with Epstein-Barr virus (EBV) and human cytomegalovirus (CMV)

针对疱疹病毒感染的细胞免疫：EB 病毒 (EBV) 和人类巨细胞病毒 (CMV) 的研究

• 批准号: G0901755-E02/1
• 负责人: Paul Moss
• 金额: $ 263.33万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0901755-E02%2F1
• 关键词: Cellular; immunity; herpesvirus; infections; studies

Human herpes viruses are a group of eight related viruses which cause a range of diseases such as glandular fever, chicken pox and some cancers. One remarkable feature is that they are never eradicated from our bodies after infection but persist for many decades. However, these ?chronic infections? may be associated with clinical complications arising from virus-induced distortion of the immune system. Over many years we have studied the immune response to two of these viruses, Epstein Barr Virus (EBV) and Cytomegalovirus (CMV, which infect the vast majority of the human population. We have studied the immune response that develops against the viruses both in healthy donors and those who are immune-suppressed.We now propose to continue our work in three main areas. Firstly, we will study how a major component of the immune response, T cells, control the viruses. We will focus on which viral proteins are ?seen? by the T cells and how this is related to proteins the virus makes to evade immunity. We will determine which responses survive over time and the mechanisms behind this. We will also study how immunity is maintained in elderly individuals and which factors underlie the potentially damaging expansion of the immune response in some elderly people.Secondly we will make a detailed study of the proteins that the virus makes in order to suppress the immune response such that it can survive. This is important to understand both the profile of immune response that is observed and also how we may improve this in the future.Thirdly, we will study the balance between the virus and the immune response, as seen in healthy people and in patients, to understand the effect of these viruses on the general immune function of the population. We will determine what level of virus different people are carrying, whether the level is stable over rtime and how this determines the nature of the immune response. We will study how single infection with either EBV or CMV, or dual infection with both viruses, influences the immune system, and how anti-viral drugs might improve immune function.Overall this work should provide the most detailed analysis of the interaction between our immune systems and herpesviruses. EBV and CMV are increasingly recognised as major global pathogens and our programme is an important opportunity to determine the factors and mechanisms that contribute to viral disease.

人类疱疹病毒是一组八种相关病毒，可引起一系列疾病，如腺热，水痘和一些癌症。一个显着的特点是，它们在感染后从未从我们的身体中根除，而是持续数十年。然而，这些？慢性感染？可能与由病毒诱导的免疫系统扭曲引起的临床并发症有关。多年来，我们已经研究了对这些病毒中的两种的免疫应答，即感染绝大多数人群的爱泼斯坦巴尔病毒（EBV）和巨细胞病毒（CMV）。我们已经研究了健康捐赠者和免疫抑制者针对病毒产生的免疫反应。我们现在建议在三个主要领域继续我们的工作。首先，我们将研究免疫反应的主要组成部分T细胞如何控制病毒。我们将重点讨论哪些病毒蛋白质？看见了吗？以及这是如何与病毒产生的逃避免疫的蛋白质相关的。我们将确定哪些反应会随着时间的推移而幸存下来，以及这背后的机制。我们还将研究老年人的免疫力是如何维持的，以及哪些因素导致了一些老年人免疫反应的潜在破坏性扩大。其次，我们将详细研究病毒为了抑制免疫反应而产生的蛋白质，以便它能够存活。这对了解所观察到的免疫反应的概况以及我们将来如何改善这一状况都很重要。第三，我们将研究病毒和免疫反应之间的平衡，如在健康人和患者中所见，以了解这些病毒对人群一般免疫功能的影响。我们将确定不同的人携带的病毒水平，该水平是否随时间而稳定，以及这如何决定免疫反应的性质。我们将研究EBV或CMV单次感染或两种病毒的双重感染如何影响免疫系统，以及抗病毒药物如何改善免疫功能。总体而言，这项工作应该提供我们的免疫系统和疱疹病毒之间相互作用的最详细的分析。EBV和CMV越来越被认为是全球主要的病原体，我们的项目是确定导致病毒性疾病的因素和机制的重要机会。