Immunopathogenesis of varicella zoster virus infection

水痘带状疱疹病毒（VZV）是一种疱疹病毒，感染高达90%的人口。VZV主要在儿童期引起水痘（水痘），在中老年人中引起带状疱疹（带状疱疹）。虽然VZV通常在健康个体中引起相对轻微的疾病，但VZV仍然在儿童和成人中引起显著的发病率。VZV在免疫功能低下的个体中引起危及生命的疾病，例如老年人或患有HIV疾病的患者。带状疱疹影响许多老年人，主要并发症是长期的剧烈疼痛或带状疱疹后神经痛（PHN），这可能会使人严重衰弱，并且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，但人们对这种病毒如何发挥作用和引起疾病知之甚少。该项目旨在提高我们对VZV感染如何影响专门的人类细胞的理解，以便为开发旨在减轻VZV疾病对社区影响的疗法提供新的信息。该项目有四个组成部分：（1）我们将继续研究表明VZV导致人类皮肤细胞（成纤维细胞）而不是人类神经细胞（神经元）的程序性细胞死亡（凋亡）。我们的目标是鉴定负责人类神经元和成纤维细胞凋亡的细胞类型特异性调节的病毒基因（2）我们将检查人类感觉神经节（3）评估VZV感染对特化免疫细胞能力的影响，我们已经证明VZV可以通过干扰树突状细胞的功能来主动避免免疫检测。我们的目标是确定病毒干扰免疫分子表达的机制，这些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.