Viral and host cell gene expression during the establishment and maintenance phases of human cytomegalovirus latency

人巨细胞病毒（CMV）是一种疱疹病毒，感染大多数人口。HCMV是新生儿和免疫抑制人群中严重、危及生命的疾病的重要原因。移植受者，如骨髓，肾脏和心脏移植患者，特别是在发展CMV疾病的风险。与其他疱疹病毒一样，CMV在初次感染后可以建立终身潜伏感染。在潜伏期，病毒在人体内保持休眠状态，不会产生传染性病毒。然而，当条件合适时，病毒可以从潜伏状态中唤醒（即重新激活），产生新的传染性病毒和疾病。在免疫抑制的个体如移植患者中，病毒潜伏期和再活化是最受医学关注的，但对病毒潜伏期的了解仍然非常少。这些研究的总体目标是更好地了解CMV潜伏期是如何建立和维持的，最终目标是推进抗病毒疗法的设计，以破坏这些过程。该项目有三个主要组成部分：第一，我们的目标是确定和检测潜伏期建立过程中的病毒基因表达，这些发现将对我们理解潜伏期产生深远的影响。其次，我们将研究当人类细胞被潜伏感染时，它们是如何受到影响的。一种新的和令人兴奋的技术称为DNA微阵列，现在可以检查成千上万的基因的表达在一个单一的实验。这是第一次，我们将能够确定细胞在延迟的建立和维护阶段如何变化。第三，我们将应用微阵列技术来确定人类细胞基因是如何改变的，以响应在感染潜伏期活跃的单个病毒基因的表达。

Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing CMV disease. Like other herpesviruses, after initial infection CMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and no infectious virus is made. However, when conditions are right the virus can awaken (ie reactivate) from its latent state, producing new infectious virus and disease. It is in immunosuppressed individuals such as transplant patients that viral latency and reactivation are of most medical concern, yet viral latency remains very poorly understood. The overall aim of these studies is to provide a much better understanding of how CMV latency is established and maintained, with the ultimate goal of making advances for the design of anti-viral therapies to disrupt these processes. This project has three major components: Firstly, we aim to identify and characterise viral gene expression during the establishment of latency and these findings will have profound implications to our understanding of latency. Secondly, we will examine how human cells are affected when they become latently infected. A new and exciting technology called DNA microarray now makes it possible to examine the expression of many thousands of genes in a single experiment. For the first time, we will be able to determine how the cell changes during the establishment and maintenance phases of latency. Thirdly, we will apply microarray technologies to determine how human cell genes are altered in response to the expression of individual viral genes that are active during the latent phase of infection.