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

人巨细胞病毒(CMV)是一种感染大多数人群的疱疹病毒。巨细胞病毒是新生儿和免疫抑制人群中严重威胁生命的疾病的重要原因。骨髓、肾脏和心脏移植患者等移植受者患巨细胞病毒病的风险尤其大。像其他疱疹病毒一样，CMV在最初感染后可以建立终身潜伏感染。在潜伏期间，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唤醒(即重新激活)，产生新的传染性病毒和疾病。正是在免疫抑制的个体中，如移植患者，病毒潜伏期和重新激活是最令人关注的医学问题，但病毒潜伏期仍然知之甚少。这些研究的总体目的是为了更好地了解CMV潜伏期是如何建立和维持的，最终目标是为干扰这些过程的抗病毒疗法的设计取得进展。这个项目有三个主要部分：首先，我们的目标是识别和表征病毒基因在潜伏期建立过程中的表达，这些发现将对我们理解潜伏期有深远的影响。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。一种名为DNA微阵列的新的令人兴奋的技术现在使在一次实验中检查数千个基因的表达成为可能。我们将第一次能够确定细胞在潜伏期的建立和维护阶段是如何变化的。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，以回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.