Determination of the mechanisms of action of a cytomegalovirus chemokine receptor homologue in pathogenesis

确定巨细胞病毒趋化因子受体同源物在发病机制中的作用机制

• 批准号: nhmrc : 456137
• 负责人: A/Pr Nicholas Davis-Poynter
• 金额: $ 16.76万
• 依托单位: The University of Queensland
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/determination-mechanisms-action-homologue-pathogenesis/82741
• 关键词: Determination; mechanisms; action; cytomegalovirus; chemokine

A number of herpesviruses encode proteins that are similar to proteins of our immune system. These pirated proteins are exploited by the virus to enable it to replicate and persist in the infected individual, usually by evading or gaining advantage from the normal immune response. This project will investigate the role of one such protein found in both human and animal herpesviruses (specifically cytomegaloviruses (CMV)) that is conserved with cellular cell surface proteins (receptors) that bind immune signaling molecules (chemokines). Chemokines are important proteins in the early response to infection. Binding of chemokines to their receptors initiates a cascade of signals within the cell that has profound effects on cellular responses to environmental stimuli. Thus, it is believed that herpesviruses have acquired chemokine receptors to modify or react to the immune response, causing infected cells to behave abnormally either despite or in response to chemokine signals. This project will determine how this CMV specific protein affects the function of cells that CMV infects and how this may promote virus replication, dissemination and persistence in infected hosts. We will also engineer CMVs where the activity of the target protein can be inhibited by administration of prototype antiviral drugs. If inhibition of the activity of the protein is found to reduce virus replication, dissemination or persistence, then this will demonstrate that this type of protein would be a suitable target for the development of novel drugs active against CMV infections. CMV can cause serious (potentially life threatening) disease in newborn children (following infection in the uterus) and immunosuppressed people (eg. organ transplant recipients and people with HIV-AIDS). Our studies will improve our understanding of the contribution of a specific CMV protein to disease, thereby assisting efforts to reduce the impact of CMV infections.

许多疱疹病毒编码的蛋白质与我们免疫系统的蛋白质相似。这些被盗版的蛋白质被病毒利用，使其能够在感染者体内复制并持续存在，通常是通过避开或从正常的免疫反应中获得优势。该项目将研究在人类和动物疱疹病毒(特别是巨细胞病毒(CMV))中发现的一种与结合免疫信号分子(趋化因子)的细胞表面蛋白(受体)保守的蛋白质的作用。趋化因子是感染早期反应中的重要蛋白质。趋化因子与其受体的结合在细胞内启动了一系列信号，对细胞对环境刺激的反应产生了深远的影响。因此，人们认为疱疹病毒已经获得了趋化因子受体来改变或对免疫反应做出反应，导致感染的细胞无论是对趋化因子信号还是对趋化因子信号的反应都会出现异常行为。该项目将确定这种CMV特定蛋白如何影响CMV感染的细胞的功能，以及如何促进病毒在受感染宿主中的复制、传播和持久性。我们还将设计CMV，其中目标蛋白的活性可以通过给予原型抗病毒药物来抑制。如果发现抑制蛋白的活性可以减少病毒的复制、传播或持久性，那么这将证明这种类型的蛋白将是开发抗CMV感染的新药的合适靶点。巨细胞病毒可导致新生儿(在子宫感染后)和免疫抑制者(例如。器官移植接受者和艾滋病毒/艾滋病患者)。我们的研究将提高我们对特定CMV蛋白对疾病的贡献的理解，从而有助于减少CMV感染的影响。