Viral interference with apoptosis: defining the mechanisms and effects on viral pathogenesis

病毒干扰细胞凋亡：定义病毒发病机制和影响

• 批准号: nhmrc : 458746
• 负责人: Dr Christopher Andoniou
• 金额: $ 36.76万
• 依托单位: The University of Western Australia
• 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/viral-interference-apoptosis-viral-pathogenesis/80870
• 关键词: Viral; interference; apoptosis; defining; mechanisms

Apoptosis, or programmed cell death, is an orderly process whereby unwanted or damaged cells are removed from an organism. Deregulation of apoptosis has been implicated in the development of diseases such as cancer and autoimmunity. Therefore, a precise understanding of the mechanisms controlling the initiation of apoptosis has important clinical implications. In addition to removing unwanted cells, apoptosis functions as a defence mechanism to inhibit viral replication. Hence, in order to replicate efficiently viruses have evolved means to inhibit or interfere with apoptosis. The central aim of this work is to understand how two genes encoded by murine cytomegalovirus (MCMV) inhibit apoptosis and contribute to viral replication. MCMV is used as a model for human CMV (HCMV) infection. The majority of the human population is infected with HCMV which poses no risk to healthy individuals. However, reactivation of HCMV in people who are immunosuppressed such as transplant recipients or AIDS patiens is a significant cause of mortality. The MCMV infection model has provided important insights as to how the immune system controls infection and the mechanisms utilized by viruses to circumvent these processes. The proposed studies will improve our understanding of the processes that regulate viral replication. Understanding how viruses subvert host defence mechanisms will allow us to better understand their role in causing human disease, and thus, will provide key information for the design of improved anti-viral strategies. Importantly, the type of analyses proposed here will also contribute critical insights into the normal processes that control cell survival.

细胞凋亡，或程序性细胞死亡，是一个有序的过程，其中不需要的或受损的细胞从生物体中去除。细胞凋亡的失调与疾病如癌症和自身免疫的发展有关。因此，精确理解细胞凋亡启动的控制机制具有重要的临床意义。除了去除不需要的细胞外，细胞凋亡还作为一种防御机制来抑制病毒复制。因此，为了有效地复制，病毒已经进化出抑制或干扰细胞凋亡的手段。这项工作的中心目的是了解两个基因编码的小鼠巨细胞病毒（MCMV）抑制细胞凋亡，并有助于病毒复制。MCMV用作人CMV（HCMV）感染的模型。大多数人感染了HCMV，但对健康个体没有风险。然而，在免疫抑制的人如移植受体或AIDS患者中，HCMV的再活化是死亡的重要原因。MCMV感染模型为免疫系统如何控制感染以及病毒规避这些过程的机制提供了重要的见解。拟议的研究将提高我们对调节病毒复制过程的理解。了解病毒如何破坏宿主防御机制将使我们能够更好地了解它们在引起人类疾病中的作用，从而为设计改进的抗病毒策略提供关键信息。重要的是，本文提出的分析类型也将有助于对控制细胞存活的正常过程的关键见解。