Mechanisms of immune modulation by human cytomegalovirus during the latent phase of infection

人巨细胞病毒（CMV）是一种疱疹病毒，感染大多数人口。CMV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。骨髓和实体器官移植受者特别容易发生严重的CMV疾病。CMV具有在宿主的生命中以休眠或潜伏形式隐藏在体内的显着能力。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。在免疫抑制的个体中，如移植患者，潜伏期的再激活具有最重要的医学意义，但对感染的潜伏期仍然知之甚少。我们最近报道，在潜伏感染期间，CMV干扰在我们的免疫系统中起关键作用的蛋白质的表达。这种蛋白质被称为MHC II类，其正常功能对我们的免疫系统对抗感染至关重要。因此，我们假设CMV成功隐藏在潜伏状态的细胞中的能力至少部分是由于其干扰细胞正确制造MHC II类蛋白的能力。该项目旨在进一步定义和验证潜伏CMV的功能，使其能够干扰我们的免疫系统。首先，我们的目标是继续我们的研究，以确定潜在的CMV干扰MHC II类表达的机制。其次，我们将试图确定潜伏的CMV是否会干扰我们免疫系统的任何其他重要组成部分。第三，我们将寻求确定导致干扰MHC II类表达的精确病毒基因。确定免疫系统调节的机制和负责这种干扰的病毒基因可能会导致基因治疗的设计，以减轻CMV疾病对移植受者的临床影响。

Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. CMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Bone marrow and solid organ transplant recipients are particularly at risk of developing serious CMV disease. CMV has the remarkable ability to hide in the body in a dormant or latent form for the life of the host. 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 reactivation from latency is of most medical significance, yet the latent phase of infection remains very poorly understood. We recently reported that during latent infection CMV interfered with the expression of a protein which plays a crucial role in our immune system. This protein is called MHC class II and its proper function is essential for our immune system to fight infections. Thus, we postulated that the ability of CMV to successfully hide in a cell in a latent state is at least partially due to its ability to interfere with the cells ability to properly make MHC class II proteins. This project aims to futher define and characterise the functions of latent CMV that enable it to interfere with our immune system. Firstly, we aim to continue with our studies to determine the mechanism by which latent CMV interferes with MHC class II expression. Secondly, we will seek to determine whether latent CMV interferes with any other important components of our immune system. Thirdly, we will seek to identify the precise viral gene that causes the interference with MHC class II expression. Determining the mechanism of immune system regulation and the viral gene(s) responsible for this interference may lead to the design of gene therapies to lessen the clinical impact of CMV disease in transplant recipients.