Molecular mechanisms of caveolin-1 controlled infection of endothelial cells by Influenza A and Ebola viruses

• Applicant: Professor Dr. Hans-Joachim Schnittler
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2002 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5389569

The proposed project deals with the molecular mechanisms leading to disturbances of endothelial cells in viral hemorrhagic fever (VHF) caused by Ebola and influenza A viruses. Three pathogen determinants are addressed. Firstly, we will use the influenza fowl plague virus, which is strictly endothelial tropic to investigate direct virus induced disturbances of endothelial structure and barrier function. Secondly, we will clarify whether or not recombinant soluble glycoproteins (sGP, GP1 and delta peptide) of Ebola viruses disturb endothelial cells. Thirdly, we will uncover in detail the influence of host cell factors that are released from Ebola virus and Marburg virus infected monocytes/macrophages on endothelial barrier function. Using functional (shear stress, impedance spectroscopy) biochemical, morphological and molecular biological techniques we draw attention to proteins of the intercellular junctions, focal contacts and cytoskeleton. Fluorescent fusion proteins expressed in cell lines and endothelial cells will be used to follow the fate of particular host cell proteins under the influence of the different pathogen determinants. The investigations will lead to identification of the proteins and mechanisms responsible for endothelial disturbances and might help to design therapeutic agents and the development of preventative strategies in VHF.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1130: Infections of the Endothelium