Defining the molecular effectors and regulators of anti-viral immune responses

在人类中，巨细胞病毒感染可导致严重疾病，甚至可能在免疫系统不成熟或受损的个体中是致命的，如新生儿、艾滋病患者、移植受体和接受化疗药物治疗的人。然而，大多数健康个体可以以最小的疾病清除感染。巨细胞病毒引起疾病的能力在缺乏有效的免疫应答的情况下增加，这种免疫应答通常会在疾病发生前清除病毒。因此，了解抗病毒免疫应答的特异性介质的作用对于建立设计更有效的抗病毒疗法的指南至关重要。巨细胞病毒感染的小鼠模型提供了一个独特的系统来剖析病毒感染过程中免疫应答的特定组分的作用。我们以前的研究表明，抗病毒免疫反应是复杂的，涉及众多参与者。本提案中工作的中心目标是确定抗病毒免疫应答的特定分子效应物和调节物的精确贡献，并确定它们在病毒感染的不同阶段的相关性。因此，这些研究的结果将有助于了解人类巨细胞病毒感染的发病机制，更重要的是，将为合理设计改进的抗病毒药物和疫苗提供重要的见解。由于研究中的分子和细胞也被认为在控制肿瘤生长和移植存活的免疫反应中起着至关重要的作用，因此拟议的研究将为开发不仅与巨细胞病毒感染相关的病理学新疗法提供有价值的见解，还与上述条件有关。

In humans, cytomegalovirus infection can cause severe disease and may even be fatal in individuals with immature or compromised immune systems, such as newborns, AIDS patients, transplant recipients and people treated with chemotherapeutic drugs. The majority of healthy individuals however can clear the infection with minimal disease. The ability of cytomegalovirus to cause disease is increased in the absence of effective immune responses which would normally clear the virus before illness occurs. Understanding the role of specific mediators of anti-viral immune responses is therefore of paramount importance in establishing the guidelines for the design of more effective anti-viral therapies. The mouse model of cytomegalovirus infection provides a unique system to dissect the roles of specific components of the immune response during the course of viral infection. Our previous studies have shown that anti-viral immune responses are complex and involve a multitude of players. The central aim of the work in the current proposal is to establish the precise contribution of specific molecular effectors and regulators of anti-viral immune responses and define their relevance during the different stages of viral infection. Hence, the results of these studies will be relevant to understanding the pathogenesis of cytomegalovirus infection in humans and more importantly will provide critical insights into the rational design of improved antiviral drugs and vaccines. Since the molecules and cells under investigation are also known to play a crucial role in immune responses that control tumour growth and transplant survival, the proposed studies will provide valuable insight towards the development of new therapies for pathologies associated not only with cytomegalovirus infection, but also with the conditions named above.