Immunopathogenesis of varicella zoster virus infection

水痘带状疱疹病毒(VZV)是一种疱疹病毒，感染人数高达90%。VZV主要在儿童时期引起水痘(水痘)，在中老年人引起带状疱疹(带状疱疹)。虽然VZV通常会在健康人中引起相对轻微的疾病，但VZV仍然会在儿童和成人中造成严重的发病率。VZV在免疫功能受损的人中会导致危及生命的疾病，例如老年人或患有艾滋病毒疾病的患者。带状疱疹影响许多老年人，主要并发症是持续的剧烈疼痛或带状疱疹后神经痛(PHN)，这可能会严重削弱身体，通常需要在首次发作后数月甚至数年的后续医疗护理。尽管它对社区产生了重大影响，但人们对这种病毒的功能和致病机理知之甚少。这个项目旨在提高我们对VZV感染如何影响专门的人类细胞的了解，以便为旨在减少VZV疾病对社区的影响的治疗方法的开发提供新的信息。该项目包括四个部分：(1)我们将继续研究表明，VZV会导致人类皮肤细胞(成纤维细胞)的程序性细胞死亡(凋亡)，但不会导致人类神经细胞(神经元)的程序性死亡。我们的目标是确定负责细胞类型特异性调节人类神经元和成纤维细胞凋亡的病毒基因(2)我们将检查带状疱疹期间的人类感觉神经节(人类神经细胞团)，并确定存在哪些免疫细胞以及神经元是否正在经历凋亡(3)评估VZV感染对特殊免疫细胞(称为树突状细胞)正常成熟能力的影响(4)我们已经证明VZV可能通过干扰树突状细胞的功能来主动躲避免疫检测。我们的目标是确定病毒干扰免疫分子表达的机制，免疫分子对我们的免疫系统至关重要。

Varicella zoster virus (VZV) is a herpesvirus which infects up to 90% of the population. VZV causes chicken pox (varicella) predominantly in childhood and shingles (herpes zoster) in middle to old age people. Whilst VZV usually causes relatively mild disease in healthy individuals, VZV still causes significant morbidity in children and adults. VZV causes life-threatening disease in immunocompromised individuals such as patients who are elderly or have HIV disease. Shingles affects many elderly individuals and a major complication is prolonged severe pain or post-herpetic neuralgia (PHN), which can be severely debilitating and often requires follow-up medical care for months or even years after the initial attack. Despite its significant impact on the community, little is known about how this virus functions and causes disease. This project aims to improve our understanding of how VZV infection affects specialised human cells in order to provide novel information for the development of therapies aimed at lessening the impact of VZV disease on the community. This project has four components: (1) We will continue studies which have shown that VZV causes programmed cell death (apoptosis) in human skin cells (fibroblasts) but not human nerve cells (neurons). We aim to identify viral genes responsible for the cell-type specific modulation of apoptosis in human neurons and fibroblasts (2) We will examine human sensory ganglia (clusters of human nerve cells) during shingles and determine what immune cells are present and whether neurons are undergoing apoptosis (3) To assess the impact of VZV infection on the ability of specialized immune cells (called dendritic cells) to mature properly (4) We have shown that VZV may actively avoid immune detection by interfering with the function of dendritic cells. We aim to identify the mechanism responsible for the virus interfering with the expression of immune molecules which are essential for our immune system.