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

人类疱疹病毒是由八种相关病毒组成的一组，它们会引起一系列疾病，如腺热、水痘和某些癌症。一个显著的特点是，它们在感染后永远不会从我们的身体中根除，而是会持续数十年。然而，这些呢？慢性感染?可能与由病毒引起的免疫系统畸变引起的临床并发症有关。多年来，我们研究了对其中两种病毒的免疫反应，爱泼斯坦巴尔病毒（EBV）和巨细胞病毒（CMV），这两种病毒感染了绝大多数人。我们研究了健康捐献者和免疫抑制者对病毒产生的免疫反应。我们现在建议继续在三个主要领域开展工作。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。我们将重点关注哪些病毒蛋白被看到？以及这与病毒制造的逃避免疫的蛋白质之间的关系。我们将确定哪些反应会随着时间的推移而存活下来，以及背后的机制。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某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产生的蛋白质，以抑制免疫反应，使其能够存活。这对于了解所观察到的免疫反应的概况以及我们将来如何改进这一点都很重要。第三，我们将研究病毒和免疫反应之间的平衡，正如在健康人群和患者中看到的那样，以了解这些病毒对人群总体免疫功能的影响。我们将确定不同的人携带的病毒水平，这种水平是否长期稳定，以及这如何决定免疫反应的性质。我们将研究EBV或CMV的单一感染，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。总的来说，这项工作应该为我们的免疫系统和疱疹病毒之间的相互作用提供最详细的分析。EBV和CMV越来越被认为是全球主要的病原体，我们的计划是确定导致病毒性疾病的因素和机制的重要机会。

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.