The impact of interplays between viral immune evasion proteins and host cell-surface receptors on viral pathogenesis

疱疹病毒可引起终身感染。这些病毒进化出一系列机制来逃避宿主的免疫反应，否则这些免疫反应就会消灭它们。巨细胞病毒是疱疹病毒家族中充满避免免疫反应的方法的成员之一。这种病毒虽然不会在健康人中引起症状，但在免疫抑制的个体中，如艾滋病患者或接受移植的人，或免疫反应发育不良的新生儿中，它是疾病和死亡的重要原因。在目前的项目中，我们将探索病毒编码的蛋白是如何与一种名为自然杀伤细胞(Natural Killer，NK)的免疫效应细胞上表达的细胞表面受体结合，从而干扰这些细胞的功能的。我们将寻求确定与这些病毒蛋白特异性结合的NK细胞蛋白，并对这些病毒基因进行缺失突变，以评估敲除这些基因对病毒引起的疾病有什么影响。这些研究将为病毒免疫逃避的新机制提供重要的见解，并可能为如何开发干扰这些病毒蛋白功能的治疗方法提供见解。

Herpesviruses can cause infections that persist for the lifetime of the individual. These viruses have evolved a range of mechanisms to evade the host's immune response that would otherwise eliminate them. One member of the herpesvirus family that is replete with methods for avoiding the immune response is cytomegalovirus. This virus, while not causing symptoms in healthy people, is a significant cause of disease and mortality in indivuals who are immunosuppressed such as AIDS patients or people undergoing transplantation, or in neonates who have poorly developed immune responses. In the current project we will explore how virally encoded proteins that bind to cell surface receptors expressed on a class of immune effector cell called the Natural Killer (NK) cell, can interfere with the functions of these cells. We will seek to define the NK cell proteins that are specifically bound by these viral proteins and also make deletion mutants of these viral genes to assess what effect knocking out these genes has on virus-caused disease. These studies will provide important insights into novel mechanisms of viral immune evasion and may provide insights into how therapies could be developed that interfere with the functions of these viral proteins.