Analysis of viral and cellular gene expression during human cytomegalovirus latent infection of hematopoietic cells

人巨细胞病毒潜伏感染造血细胞过程中病毒和细胞基因表达分析

• 批准号: nhmrc : 153873
• 负责人: A/Pr Barry Slobedman
• 金额: $ 27.18万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/analysis-viral-cellular-hematopoietic-cells/100701
• 关键词: Analysis; viral; cellular; gene; expression

Human cytomegalovirus (HCMV) 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 HCMV disease. Like other herpesviruses, after initial infection HCMV 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. This project has three major components. Firstly, we aim to continue studies which are defining what viral genes are active (ie expressed) during latent infection. Identification of these genes and determination of how they function may 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 latency and reactivation. The study of viral and cellular gene expression during latency may contribute to the development of drugs which interfere with the viruses ability to become latent or reactivate. Thirdly, we have preliminary results which suggest that latent HCMV may actively avoid detection by the immune system. In this project we also aim to determine the mechanism by which the virus interferes with the expression of molecules which are an essential component of our immune system.

人巨细胞病毒（HCMV）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。骨髓、肾脏和心脏移植患者等移植受者特别容易患上HCMV疾病。与其他疱疹病毒一样，HCMV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。该项目有三个主要组成部分。首先，我们的目标是继续研究，确定哪些病毒基因在潜伏感染期间是活跃的（即表达）。识别这些基因并确定它们的功能可能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。我们将首次能够确定细胞在延迟和重新激活期间如何变化。对潜伏期病毒和细胞基因表达的研究可能有助于开发干扰病毒潜伏或再活化能力的药物。第三，我们有初步的结果表明，潜伏的HCMV可以主动避免免疫系统的检测。在这个项目中，我们还旨在确定病毒干扰分子表达的机制，这些分子是我们免疫系统的重要组成部分。