Unraveling the molecular mechanisms of Hantavirus assembly

汉坦病毒（HV）可引起危及生命的人类人畜共患病，致死率高达50%。在德国也观察到周期性的艾滋病毒暴发，例如在2012年，向罗伯特-科赫研究所报告了约3000例病例。到目前为止，这种疾病的治疗只有症状，还没有特定的抗病毒方法，这可能是因为在分子水平上对感染过程缺乏深入的了解。需要定量地了解控制艾滋病毒复制的详细机制，以便预防和治疗该疾病未来的大流行暴发。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），这些相互作用涉及在感染细胞中组装新病毒粒子。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的多聚和复合物的形成，作为细胞内定位的功能。由此获得的知识很可能对理解HV组装和从宿主细胞中退出的分子基础具有很大价值。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。

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.