Phenotypical and functional modulation of B-lymphocytes by KSHV infection

疱疹病毒在普通人群中广泛传播。在大多数情况下，它们只会引起无害的儿童感染。然而，与其他病原体不同的是，它们不会从体内清除，而是在宿主的余生中留在特定的组织中。在某些情况下，例如在免疫功能低下的患者中，它们能够重新激活并引起危及生命的疾病。为了实现在宿主体内的终身存留，疱疹病毒发展了多种措施来应对其免疫系统。与其他病毒不同的是，它们表达大量（大约70到170种）不同的蛋白质，其中大多数蛋白质的功能尚未得到表征。很大比例的疱疹病毒蛋白参与操纵宿主及其免疫系统。在这个项目中，我们将专注于一种叫做？卡波西肉瘤相关疱疹病毒？（KSHV）引起皮肤肿瘤和淋巴瘤，主要发生在免疫功能低下的个体中，例如艾滋病患者。这种疱疹病毒感染的细胞对免疫系统非常重要，因为它们能够产生抗体，即b淋巴细胞。感染KSHV会严重改变b淋巴细胞，使正常情况下可在表面发现的蛋白质消失。由于这种表面蛋白的消除，被感染的细胞不能再被免疫系统识别和杀死。我们将试图阐明导致kshv感染细胞改变和b淋巴细胞表面蛋白消失的机制。特别是，我们将寻找那些负责操纵b淋巴细胞的病毒蛋白。如果我们了解KSHV如何改变被感染的细胞，我们将能够开发出新的药物来破坏这些机制，这样病毒就不能再躲避免疫系统，并从体内被消灭。此外，通过了解这些机制，我们将能够将它们用作治疗旨在抑制免疫系统的疾病的工具，例如自身免疫性疾病，并将它们应用于未来的疫苗接种和基因治疗方法。

Herpesviruses are widely spread throughout the general population. In most cases, they only cause harmless childhood infections. In contrast to other pathogens, however, they are not eliminated from the body but rather stay in specific tissues for the rest of the life of the host. Under certain conditions, for example in immunocompromised patients, they are able to reactivate and cause life-threatening diseases. To achieve the life-long persistence in the host, herpesviruses developed a variety of measures to cope with its immune system. In contrast to other viruses, they express a large number (between approximately 70 and 170) of different proteins, most of which have not been characterized yet in terms of their function. A very large percentage of herpesviral proteins are involved in manipulating the host and its immune system. In this project, we will focus on a herpesvirus called ?Kaposi Sarcoma associated Herpesvirus? (KSHV) which causes skin tumors and lymphomas, predominantly in immuncompromised individuals as for example in AIDS patients. This herpesvirus infects cells which are very important for the immune system since they are able to produce antibodies, so-called B-lymphocytes. The infection with KSHV alters B-lymphocytes severely and has the effect that proteins which normally can be found on the surface disappear. Due to this elimination of surface proteins the infected cells can not be recognized and killed by the immune system any more. We will try to elucidate the mechanisms leading to an alteration of KSHV-infected cells and the disappearance of B-lymphocyte surface proteins. Particularly, we will search for those viral proteins which are responsible for the manipulation of B-lymphocytes. If we understand how KSHV alters infected cells, we will be able to develop new drugs which disrupt these mechanisms so that the virus can not hide from the immune system any more and is eliminated from the body. Moreover, by understanding these mechanisms we will be able to use them as tools in diseases in which a suppression of the immune system is intended, for example in auto-immune diseases, and apply them in future approaches in vaccination and gene therapy.