Two types of autophagy in pathogenesis and antigen presentation of Herpes Simplex Virus type 1

1型单纯疱疹病毒（HSV1）在世界上约70 - 80%的人口中流行，引起从唇疱疹到危及生命的脑炎等不同严重程度的疾病，并与阿尔茨海默病的进展有关。此外，眼睛感染1型单纯疱疹病毒是非洲最常见的致盲原因，在北美和欧洲也很普遍。人们对这种病毒是如何被免疫系统控制的仍然知之甚少。我建议分析特异性抗病毒免疫细胞（杀伤细胞）如何识别HSV1感染的细胞。特别是，我想找出一种叫做自噬（自食）的细胞过程是如何导致这种情况的。自噬参与营养物质的循环、细胞内病原体的清除和适应性抗病毒免疫。我的宿主实验室最近描述了这一途径对杀伤细胞免疫识别的贡献。除了细胞质自噬外，他们还观察到一种新的核自噬途径。这种替代性自噬途径的组成和分子机制迄今尚不清楚。更好地了解这种新型自噬途径的机制以及两种类型的自噬对抗病毒免疫的贡献，可能会导致针对这种病毒和相关疱疹病毒的新型药物的开发。此外，它可能允许操纵患者的免疫系统，要么通过增强免疫反应以更快地从严重感染中恢复，要么通过下调接受疱疹病毒感染器官移植的患者的免疫反应。

Herpes simplex virus type 1 (HSV1) is endemic in about 70 - 80% of the world's population, causes diseases varying in severity from cold sores to life threatening encephalitis, and is implicated in the progression of Alzheimers disease. Furthermore, a HSV1 infection of the eyes is the most common cause of blindness in Africa, and widespread in North America and Europe. How this virus is controlled by the immune system is still little understood. I propose to analyse how specific antiviral immune cells (killer cells) recognise HSV1 infected cells. In particular, I want to find out how a cellular process termed autophagy (self-eating) contributes to this. Autophagy is involved in the recycling of nutrients, the clearance of intracellular pathogens and adaptive antiviral immunity. A contribution of this pathway to immune recognition by killer cells has recently been described by my host laboratory. In addition to cytosolic autophagy, they observed a novel nuclear autophagy pathway. The components and molecular mechanism of this alternative autophagy pathway are so far unknown. A better understanding of the mechanism of this novel autophagy pathway and the contribution of both types of autophagy to antiviral immunity might lead to the development of novel drugs against this virus and related herpesviruses. Furthermore, it might allow a manipulation of the immune system of patients, either by enhancing the immune response for faster recovery from severe infections, or by downregulating the immune response in patients that are receiving a herpesvirus-infected organ transplant.