The role of ebola virus glycoproteins in the disturbance of the endothelium

• Applicant: Ute Ströher
• Subject Area: Virology
• Term: from 2002 to 2003
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5390288

Marburg and Ebola viruses cause a fulminant hemorrhagic fever in humans and non-human primates. Following initially unspecific symptoms, patients display an increase in paraendothelial permeability, hypotension, coagulation disorders, and hemorrhages. Disturbances of the blood tissue barrier, primarily controlled by endothelial cells, and immunosuppression seem to be the pathogenic key factors of the disease. The endothelium is affected by two ways; directly by virus infection, which leads to activation and lytic replication, and indirectly, by a mediator-induced inflammatory response. These mediators originate from virus-activated cells of the mononuclear phagocytic system, especially macrophages, which are the primary target cells. The viral glycoproteins seem to be key factors for determining viral pathogenicity. Ebola viruses have developed specific strategies to express several products from their glycoprotein gene. The primary product is a small soluble glycoprotein precursor, which is subsequently proteolytically processed into sGP and delta-peptide. RNA editing allows the expression of the transmembrane glycoprotein GP, which mediates the spread of infection by binding to and initiating fusion with target cells. Based on current data one can postulate that besides GP, which mediates virus entry, the different soluble glycosylated products (GP1, sGP, and delta-peptide) are important determinants in pathogenicity.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1130: Infections of the Endothelium
• International Connection: Canada
• Participating Person: Privatdozent Dr. Heinrich Ulrich Feldmann