Unraveling the molecular mechanisms of Hantavirus assembly

揭示汉坦病毒组装的分子机制

• 批准号: 407961559
• 负责人: Professor Dr. Salvatore Chiantia
• 金额: --
• 依托单位: Institut für Biochemie und Biologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/407961559?language=en
• 关键词: Unraveling; molecular; mechanisms; Hantavirus; assembly

Hantaviruses (HV) can cause life-threatening human zoonoses with fatality rates up to 50%. Periodic HV outbreaks are also observed in Germany, with ca. 3000 cases being reported to the Robert-Koch-Institute e.g. in 2012. Treatment of the disease is so far only symptomatic and no specific antiviral approach exists yet, probably because of the lack of deep understanding of the infection process at a molecular level. The detailed mechanisms governing HV replication need to be quantitatively understood, in order to prevent and treat future pandemic outbreaks of the disease. The project described in this proposal aims at clarifying the key interactions between viral components (i.e. protein-protein and protein-lipid interactions) which are involved in the assembly of new virions in infected cells. Specifically, we will quantitatively investigate the interactions among HV glycoproteins Gn and Gc, during virus assembly, directly in living cells. To this end, we will use advanced fluorescence microscopy methods to monitor Gn and Gc multimerization and complex formation, as a function of intra-cellular localization. The knowledge thus acquired is most likely to be of great value for understanding the molecular basis of HV assembly and exit from host cells. Such knowledge will also be a pre-requisite for future rational designing of methods to interfere with the HV replication cycle.

汉坦病毒（HV）可引起危及生命的人畜共患病，病死率高达50%。在德国也观察到周期性HV暴发，其中约例如，2012年向罗伯特-科赫研究所报告了3000例病例。迄今为止，该病的治疗仅是对症治疗，还没有具体的抗病毒方法，这可能是因为缺乏对分子水平上的感染过程的深入了解。控制HV复制的详细机制需要定量地了解，以预防和治疗该疾病未来的大流行爆发。本提案中描述的项目旨在阐明病毒组分之间的关键相互作用（即蛋白质-蛋白质和蛋白质-脂质相互作用），这些相互作用参与受感染细胞中新病毒体的组装。具体来说，我们将定量研究HV糖蛋白Gn和Gc之间的相互作用，在病毒组装过程中，直接在活细胞中。为此，我们将使用先进的荧光显微镜方法来监测Gn和Gc多聚化和复合物的形成，作为细胞内定位的功能。由此获得的知识对于理解HV组装和从宿主细胞退出的分子基础最有可能具有重要价值。这些知识也将是未来合理设计干扰HV复制周期的方法的先决条件。