Modulation of apoptosis by cytomegalovirus: analysis of new mechanisms to interfere with cytomegalovirus-induced disease

巨细胞病毒对细胞凋亡的调节：干扰巨细胞病毒诱导疾病的新机制的分析

• 批准号: nhmrc : 110288
• 负责人: Prof Mariapia Degli-Esposti
• 金额: $ 46.48万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2000
• 资助国家: 澳大利亚
• 起止时间: 2000-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/modulation-apoptosis-cytomegalovirus-induced-disease/76143
• 关键词: Modulation; apoptosis; cytomegalovirus; analysis; new

Apoptosis, or programmed cell death is an essential process in developmental and homeostatic control of complex biological systems. In addition to these primary house keeping roles, apoptosis provides a powerful defence mechanism against invading pathogens, such as viruses, since it allows early elimination of infected cells from the host. A basic property of herpesviruses is their ability to establish persistent infection and remain in association with the host for its lifetime. This strongly underlines their success at reaching an accommodation with the immune system's anti-apoptotic mechanisms. The central hypothesis of this project is that herpesviruses, such as murine and human cytomegalovirus, encode proteins that interfere with cell death pathways thereby circumventing host defence so that viral replication and dissemination can proceed. Thus, the aims are to identify and characterise cytomegalovirus proteins that modulate apoptosis. These studies will improve our understanding of the control of apoptosis during viral infection, especially as caused by cytomegaloviruses. Human cytomegalovirus (HCMV) is a pathogen able to cause significant morbidity and mortality in individuals with immature or compromised immune systems, such as newborns, AIDS patients, transplant recipients and people treated with chemotherapeutic drugs. Hence, the proposed studies will allow the elucidation of molecular mechanisms that may be relevant to the pathogenesis of HCMV in man and will provide insights into the rational design of suitable antiviral drugs and vaccines. Understanding viral mechanisms of host immune evasion continues to improve our understanding of complex cellular pathways. Therefore, given that abnormal regulation of apoptosis is implicated in the development of degenerative conditions, cancer and autoimmune disease, the proposed studies will provide valuable insight towards the development of new therapies for these pathological conditions.

细胞凋亡或程序性细胞死亡是复杂生物系统发育和稳态控制的重要过程。除了这些主要的管家作用之外，细胞凋亡还提供了一种强大的防御机制来抵御入侵的病原体，如病毒，因为它允许从宿主中早期消除受感染的细胞。疱疹病毒的一个基本特性是它们建立持续感染并在其一生中与宿主保持联系的能力。这有力地强调了它们在与免疫系统的抗凋亡机制达成和解方面的成功。该项目的中心假设是疱疹病毒，如鼠和人巨细胞病毒，编码干扰细胞死亡途径的蛋白质，从而绕过宿主防御，使病毒复制和传播可以进行。因此，目的是鉴定和鉴定调节细胞凋亡的巨细胞病毒蛋白。这些研究将提高我们对病毒感染过程中细胞凋亡控制的理解，尤其是巨细胞病毒感染。人巨细胞病毒（HCMV）是能够在具有不成熟或受损的免疫系统的个体（例如新生儿、AIDS患者、移植受体和用化疗药物治疗的人）中引起显著发病率和死亡率的病原体。因此，拟议的研究将允许阐明可能与人类HCMV发病机制相关的分子机制，并将为合理设计合适的抗病毒药物和疫苗提供见解。了解宿主免疫逃避的病毒机制继续提高我们对复杂细胞途径的理解。因此，鉴于细胞凋亡的异常调节与退行性疾病、癌症和自身免疫性疾病的发展有关，所提出的研究将为开发这些病理性疾病的新疗法提供有价值的见解。