Understanding the mechanisms of cytomegalovirus induced immunosuppression: relevance to viral immunotherapies

了解巨细胞病毒诱导的免疫抑制机制：与病毒免疫疗法的相关性

• 批准号: nhmrc : 212067
• 负责人: Dr Christopher Andoniou
• 金额: $ 31.16万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2002
• 资助国家: 澳大利亚
• 起止时间: 2002-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/understanding-mechanisms-cytomegalovirus-viral-immunotherapies/95937
• 关键词: Understanding; mechanisms; cytomegalovirus; induced; immunosuppression

Cytomegalovirus (CMV), measles and human immunodeficiency virus (HIV) are the three main human pathogens known to induce immunosuppression. The down-regulation of immune responses that characterizes a state of immunosuppression imparts the infecting pathogens the opportunity to escape immune surveillance and thus maximizes their chances to survive within their host, to replicate and be transmitted as required. The generalized immunosuppression caused by viral infection is often associated with secondary infections with unrelated viral and-or bacterial pathogens, and as such represents a serious clinical problem. In humans, cytomegalovirus infection can cause tissue damage in normal individuals and may cause severe disease and even mortality in individuals with immature or compromised immune systems, such as newborns, AIDS patients, transplant recipients and patients undergoing chemotherapy. The severe complications that occur in the latter group of patients result from the combined effects of pre-existing and viral induced immunosuppression that often lead to severe secondary opportunistic infections. In transplant recipients however, CMV induced immunosuppression, in the absence of secondary infections, can be beneficial and has been associated with improved transplant outcome. The central aim of the work in the current proposal is to investigate the cellular and viral mechanisms involved in cytomegalovirus induced immunosuppression. The proposed studies will improve our understanding of viral interference with host immune responses and hence will be relevant to understanding the pathogenesis of CMV infection in humans and more importantly will provide critical insights into the rational design of suitable antiviral drugs and vaccines.

巨细胞病毒（CMV）、麻疹和人类免疫缺陷病毒（HIV）是已知的三种主要的人类病原体，可诱导免疫抑制。免疫反应的下调是免疫抑制状态的特征，这使感染病原体有机会逃脱免疫监视，从而最大限度地提高它们在宿主体内生存、复制和传播的机会。病毒感染引起的全身性免疫抑制通常与不相关的病毒和/或细菌病原体继发感染有关，因此是一个严重的临床问题。在人类中，巨细胞病毒感染可导致正常个体的组织损伤，并可能导致免疫系统不成熟或受损的个体（如新生儿、艾滋病患者、移植接受者和接受化疗的患者）患上严重疾病，甚至死亡。后一组患者发生的严重并发症是由于预先存在的免疫抑制和病毒诱导的免疫抑制的共同作用，通常导致严重的继发性机会性感染。然而，在移植受者中，在没有继发性感染的情况下，巨细胞病毒诱导的免疫抑制可能是有益的，并且与移植结果的改善有关。本研究的中心目标是研究巨细胞病毒诱导免疫抑制的细胞和病毒机制。拟议的研究将提高我们对病毒干扰宿主免疫反应的理解，因此将与理解人类巨细胞病毒感染的发病机制有关，更重要的是将为合理设计合适的抗病毒药物和疫苗提供关键见解。