Die Rolle von UL128-131-abhängigen Endozytosemechanismen für den Endothelzelltropismus des menschlichen Cytomegalovirus (HCMV)

UL128-131依赖性内吞机制在人巨细胞病毒（HCMV）内皮细胞趋向性中的作用

• 批准号: 5388628
• 负责人: Professor Dr. Christian Sinzger
• 金额: --
• 依托单位: Institut für Virologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5388628?language=en
• 关键词: Die; Rolle; von; UL128; 131

This project is based on the hypothesis that interactions of tegument or capsid proteins of human cytomegalovirus (HCMV) with cellular proteins of the dynein/dynactin complex are critical for cell tropism differences between endotheliotropic HCMV/E strains and nonendotheliotropic HCMV/F strains. We will (1) analyze the contribution of various viral structural proteins to EC tropism by the construction of HCMV/F viruses pseudotyped with the respective HCMV/E proteins, (2) combine single virion immunofluorescence staining with differential removal of cytoskeleton components to dissect the role of actin and microtubules during viral penetration, transport towards the MTOC and delivery to the nucleus, and (3) analyze events of binding and phosphorylation/dephosphorylation between viral and cellular structural proteins by a combination of differential precipitation with 2-D gel electrophoresis and protein identification techniques. In conclusion, we expect insight into the molecular mechanisms underlying interstrain differences in the EC tropism of HCMV, with potential implications for the development of new antiviral strategies and the development of EC-targeted vaccines.

本项目基于人类巨细胞病毒（HCMV）的被膜或衣壳蛋白与动力蛋白/动力蛋白复合物的细胞蛋白的相互作用是嗜内皮型HCMV/E株和非嗜内皮型HCMV/F株之间细胞趋向性差异的关键。我们将(1)通过构建HCMV/E蛋白假型的HCMV/F病毒，分析各种病毒结构蛋白对EC趋向性的贡献；(2)结合单病毒粒子免疫荧光染色和细胞骨架成分的差异去除，剖析肌动蛋白和微管在病毒渗透、向MTOC转运和向细胞核递送过程中的作用。(3)结合差分沉淀、二维凝胶电泳和蛋白质鉴定技术，分析病毒与细胞结构蛋白之间的结合和磷酸化/去磷酸化事件。总之，我们期望深入了解HCMV株间EC趋向性差异的分子机制，这对开发新的抗病毒策略和EC靶向疫苗具有潜在的意义。