Molecular pathogenesis and virus-host cell interactions of Crimean-Congo haemorrhagic fever virus, an emerging and neglected viral zonoosis

Crimean-Congo haemorrhagic fever (CCHF), is an arthropid-borne disease in humans, associated with a servere clinical picture and a high mortality rate. CCHFV can aslo infect wild and domestic animals, but does not cause disease. To date there is no vaccine or reliable antiviral available. CCHFV is widely distributed throughout large areas of the world. Knowledge on the pathogenesis of this disease is limited because eg: I) The handling of the virus requires BSL-4 laboratory, II) there is a lack of clinical specimens, and III) there is a lack of good in vivo and in vitro models. Understandning virus-host cell interactions and the molecular pathogenesis is most important and it is necessary to design strategies for disease control i.e. develop new antivirals and vaccines. The main aims of the proposed project are to study the molecular mechanisms behind the pathogenesis of CCHFV and to study the virus-host cell interactions. To achieve these aims, there are four specific objectives: 1- Characterisation of essential cellular genes and pathways for virus infection by using haploid stem cells. 2- Examination of the mechanisms regulating cell death by CCHFV and delineation of the role of apoptosis in pathogenesis. 3- Definition and characterisation of the molecular functions of secreted pro-inflammatory cytokines and other molecules from human and natural host target cells induced by CCHFV. 4- Investigation of how the CCHFV infections affect cell migration.