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

1型单纯疱疹病毒发病机制和抗原呈递中的两种自噬

• 批准号: 194648290
• 负责人: Kerstin Radtke
• 金额: --
• 依托单位: Department of Pathology and Cell Biology
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/194648290?language=en
• 关键词: Two; types; autophagy; pathogenesis; antigen

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.

单纯疱疹病毒1型（HSV 1）在世界人口的约70 - 80%中流行，引起从唇疱疹到威胁生命的脑炎的严重程度不同的疾病，并且与阿尔茨海默病的进展有关。此外，眼睛的HSV 1感染是非洲最常见的致盲原因，在北美和欧洲也很普遍。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HSV 1感染细胞。特别是，我想找出一个被称为自噬（自食）的细胞过程是如何促成这一点的。自噬参与营养物质的再循环、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种途径对杀伤细胞免疫识别的贡献。除了胞质自噬，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成分和分子机制迄今未知。更好地理解这种新的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开发针对这种病毒和相关疱疹病毒的新型药物。此外，它可能允许操纵患者的免疫系统，通过增强免疫反应以更快地从严重感染中恢复，或者通过下调接受疱疹病毒感染的器官移植的患者的免疫反应。