Tick-borne hemorrhagic fever viruses belong to the families Bunyaviridae and Flavivirdae and circulate in nature in an enzootic tick-vertebrate-tick cycle. Interestingly, these viruses typically cause a severe hemorrhagic syndrome in humans but not in their vertebrate animal host. The pathogenesis of the disease is largely not understood due to sporadic nature of the outbreaks, the need of a BSL-4 to work with the viruses, and especially the lack of suitable animal models to study the disease. The research in my laboratory aims to understand how the viruses cause disease with special focus on the pathogenesis of Crimean-Congo hemorrhagic fever virus. We recently developed a new animal model that mimics human disease and we are currently trying to define what mechanisms lead to disease. This model also gives us the opportunity to study vaccines and antiviral countermeasures. Furthermore, we also interested to investigate the molecular determinants of virulence by comparing different Crimean-Congo hemorrhagic fever virus strains in primary human cells. In a collaborative effort with Dr. Wikel's group, we are currently establishing an in vivo feeding assay in which Hyalomma ticks, the main vector of CCHFV, will feed on our recently described mouse model of CCHF. With this assay we will emulate the natural infection cycle as closely as possible and it will be used to study the tick-virus-host interrelationship. We are especially interested to characterize the cellular and molecular immunology of the tick-host interface.