Molecular mechanisms of varicella zoster virus interactions with key target cells

水痘带状疱疹病毒（VZV）是一种疱疹病毒，可感染高达90%的人口。VZV主要引起儿童水痘（水痘）和中老年人带状疱疹（带状疱疹）。虽然VZV通常在健康人中引起相对轻微的疾病，但在儿童和成人中仍然引起显著的发病率。VZV在免疫功能低下的个体（如老年人或患有艾滋病毒的患者）中引起危及生命的疾病。带状疱疹影响许多老年人，主要并发症是长期剧烈疼痛或带状疱疹后神经痛（PHN），这两种疾病都严重使人虚弱，并且通常需要在初次发作后数月或数年的随访医疗护理。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的分子细节知之甚少。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，以便在抗病毒治疗方面取得进一步进展，并改进用于治疗或预防VZV疾病和PHN致残性并发症的疫苗设计。这个项目有四个组成部分：(1)我们将继续研究VZV可能主动逃避免疫系统的检测。我们的目标是确定机制和病毒基因负责干扰对我们的免疫系统至关重要的分子的表达。我们将确定VZV感染特异性免疫细胞（称为树突状细胞）是否会影响它们的功能和与其他免疫细胞（称为T细胞）相互作用的能力。(3)我们将研究VZV如何在人类神经细胞（神经元）中相互作用，以及感染的神经元是否会发生特殊的程序性细胞死亡（凋亡）。我们将研究不同的人类细胞在感染VZV后是如何变化的。一项名为DNA微阵列的令人兴奋的新技术现在使得在一次实验中检查数千个基因的表达成为可能。

Varicella zoster virus (VZV) is a herpesvirus which infects up to 90% of the population. VZV causes chickenpox (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 . Herpes zoster affects many ederly individuals and a major complication is prolonged severe pain or post-herpetic neuralgia (PHN), both severely debilitating and which often requires follow-up medical care for months or years after the initial attack. Despite its significant impact on the community, little is known about the molecular details of how this virus functions. This project aims to improve our understanding of how VZV infection affects specialised human cells in order to make further advances in antiviral therapies as well improve vaccine design for the treatment or prevention of VZV disease and the crippling complication of PHN. This project has four components: (1) We will continue studies which have shown that VZV may actively avoid detection by the immune system. We aim to identify the mechanism and viral genes responsible for interfering with the expression of molecules which are essential for our immune system. (2) We will determine whether VZV infection of specialised immune cells (called dendritic cells) will affect their ability to function and interact with other immune cells (called T cells). (3) We will examine how VZV interacts in human nerve cells (neurons) and whether infected neurons undergo specially programmed cell death (apoptosis). (4) We will examine how different human cells change when they are infected with VZV. A new and exciting technology called DNA microarray now makes it possible to examine the expression of many thousands of genes in one experiment.