Role of cytomegalovirus class I homologue in interference with host NK cell responses - a potential antiviral target

疱疹病毒如巨细胞病毒的一个共同特性是它们能够在其宿主中建立终身感染。在人类中，巨细胞病毒感染可导致正常个体的组织损伤，并可能导致严重疾病，甚至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。这些病毒建立持续感染并在其一生中与宿主保持联系的能力是其破坏正常宿主免疫反应的能力的结果。这是通过破坏或模仿对正常宿主防御机制至关重要的分子和/或途径的功能来实现的。研究中的病毒基因产物类似于一种细胞蛋白质，这种蛋白质对免疫细胞杀死外来和/或感染性因子的能力至关重要。我们将研究这种病毒基因产物干扰宿主对病毒病原体的第一道防线的机制。拟议的研究将提高我们对病毒逃避正常宿主免疫反应的策略的理解，从而为抗病毒药物和疫苗的合理设计提供见解。由于研究中的病毒蛋白类似于免疫细胞杀死外源或感染因子的能力所必需的细胞蛋白，因此对该蛋白作用机制的进一步理解将继续提高我们对细胞事件的理解，这些细胞事件在免疫反应中起着至关重要的作用，不仅涉及感染的控制，而且还涉及肿瘤生长和移植存活。因此，提出的研究将为开发与上述相关的病理状况的新疗法提供有价值的见解。

A common property of herpesviruses such as cytomegalovirus is their ability to establish lifelong infection in their hosts. In humans, cytomegalovirus infection can lead to tissue damage in normal individuals and may cause severe disease and 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 ability of these viruses to establish persistent infection and remain in association with the host for its lifetime is a consequence of their capacity to subvert normal host immune responses. This is achieved by destroying or mimicking the functions of molecules and-or pathways critical to normal host defence mechanisms. The viral gene product under investigation is similar to a cellular protein critical for the ability of immune cells to kill foreign and-or infectious agents. We will investigate the mechanisms by which this viral gene product interferes with the host's first line of defence against viral pathogens. The proposed studies will improve our understanding of the strategies used by viruses to escape normal host immune responses and hence provide insights into the rational design of antiviral drugs and vaccines. Since the viral protein under investigation is similar to a cellular protein essential for the ability of immune cells to kill foreign or infectious agents, an improved understanding of the mechanisms of action of this protein will continue to improve our understanding of cellular events which play a crucial role in immune responses involved not only in control of infection, but also in tumour growth and transplant survival. Thus, the proposed studies will provide valuable insight towards the development of new therapies for pathological conditions associated with the above.