Unraveling the molecular mechanisms of Hantavirus assembly

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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.