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

感染1型单纯疱疹病毒(HSV-1)会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感染后免疫逃逸的分子靶点是由HSV-1编码的糖蛋白B(GB)高表达的人类白细胞抗原-DR分子。这种病毒蛋白损害了人类白细胞抗原-DR向免疫系统呈递病毒多肽的生理作用。GB引导MHC II类分子的加工途径，从抗原提呈到通过胞外释放来处置HLA-DR分子。GB的表达强烈促进了生理外体的释放。在这个项目中，将研究病毒gB在细胞内分选和胞外分泌中的作用。我们项目的目的是解释GB如何干扰内小体的生物发生和外小体的产生。可能是分泌的gB-exosome调节免疫反应。我们想要探讨表达gB的外切体对免疫反应的影响，并确定外切体是否在感染免疫细胞的沟通中发挥作用。我们的结果可能为病毒入侵操纵细胞免疫反应提供一种新的机制。

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.