Manipulation of the Human Lymphocyte Antigen Class II Processing Pathway by Herpes Simplex Virus Encoded Glycoprotein B

单纯疱疹病毒编码糖蛋白 B 操纵人淋巴细胞抗原 II 类加工途径

• 批准号: 183381352
• 负责人: Professor Dr. Norbert Koch
• 金额: --
• 依托单位: Institut für Mikrobiologie und Biotechnologie (IfMB)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/183381352?language=en
• 关键词: Manipulation; Human; Lymphocyte; Antigen; Class

Infection with Herpes Simplex virus type 1 (HSV-1) elicits an effective immune response, but numerous viral evasion strategies prevent complete elimination of the virus. Molecular targets for immune evasion upon HSV-1 infection are HLA-DR molecules, which are high jacked by the HSV-1 encoded glycoprotein B (gB). This viral protein impairs the physiological role of HLA-DR to present viral peptides to the immune system. gB directs the MHC class II processing pathway from antigen presentation to disposal of HLA-DR molecules through exosomal release. The physiological exosomal release is strongly elevated by expression of gB. In this project the role of viral gB on intracellular sorting and on exosomal secretion will be investigated. Aim of our project is to explain how gB interferes with the biogenesis of endosomes and the generation of exosomes. It is possible that secreted gB- exosomes modulate immune responses. We want to explore the impact of gB expressing exosomes on immune reactions and determine whether exosomes play a role for communication of infected with immune cells. Our results could provide a novel mechanism how viral intrusion manipulates cellular immune responses.

1型单纯疱疹病毒（HSV-1）的感染引起有效的免疫反应，但许多病毒逃避策略阻碍了病毒的完全消除。HSV-1感染后免疫逃避的分子靶点是HLA-DR分子，该分子被HSV-1编码的糖蛋白B （gB）高劫持。这种病毒蛋白损害了HLA-DR向免疫系统呈现病毒肽的生理作用。gB通过外泌体释放引导MHC II类加工途径从抗原呈递到HLA-DR分子的处置。gB的表达强烈地提高了生理外泌体释放。本项目将研究病毒gB在细胞内分选和外泌体分泌中的作用。我们项目的目的是解释gB如何干扰内体的生物发生和外泌体的产生。分泌的gB-外泌体可能调节免疫反应。我们想探究表达gB的外泌体对免疫反应的影响，并确定外泌体是否在感染免疫细胞的通讯中发挥作用。我们的研究结果可能为病毒入侵如何操纵细胞免疫反应提供一种新的机制。