Phenotypical and functional modulation of B-lymphocytes by KSHV infection

KSHV 感染对 B 淋巴细胞的表型和功能调节

• 批准号: G0501453/1
• 负责人: Jurgen Haas
• 金额: $ 78.99万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0501453%2F1
• 关键词: Phenotypical; functional; modulation; lymphocytes; KSHV

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.

疱疹病毒在整个人群中广泛传播。在大多数情况下，它们只会引起无害的儿童感染。然而，与其他病原体相比，它们不会从体内消除，而是在宿主的余生中停留在特定组织中。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导致危及生命的疾病。为了实现在宿主体内的终身持久性，疱疹病毒开发了多种措施来科普其免疫系统。与其他病毒相比，它们表达大量（约70至170种）不同的蛋白质，其中大多数尚未被表征其功能。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，我们将集中在疱疹病毒称为？卡波西肉瘤相关疱疹病毒？KSHV（KSHV）引起皮肤肿瘤和淋巴瘤，主要在免疫受损的个体中，例如在AIDS患者中。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，即所谓的B淋巴细胞。KSHV感染会严重改变B淋巴细胞，并导致通常在表面发现的蛋白质消失。由于这种表面蛋白的消除，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感染细胞的改变和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如何改变受感染的细胞，我们将能够开发新的药物来破坏这些机制，使病毒无法隐藏在免疫系统中，并从体内消除。此外，通过了解这些机制，我们将能够将它们用作旨在抑制免疫系统的疾病的工具，例如在自身免疫疾病中，并将它们应用于疫苗接种和基因治疗的未来方法中。