title: Inhibition of Ebola virus glycoprotein-mediated cytotoxicity by targeting its transmembrane domain and cholesterol.
abstract: The high pathogenicity of the Ebola virus reflects multiple concurrent processes on infection. Among other important determinants, Ebola fusogenic glycoprotein (GP) has been associated with the detachment of infected cells and eventually leads to vascular leakage and haemorrhagic fever. Here we report that the membrane-anchored GP is sufficient to induce the detachment of adherent cells. The results show that the detachment induced through either full-length GP1,2 or the subunit GP2 depends on cholesterol and the structure of the transmembrane domain. These data reveal a novel molecular mechanism in which GP regulates Ebola virus assembly and suggest that cholesterol-reducing agents could be useful as therapeutics to counteract GP-mediated cell detachment.
authors.affiliation: Heidelberg University Biochemistry Center (BZH), 69120 Heidelberg, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Hacke
authors.affiliation: Department of Molecular Evolution, Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, 75124 Uppsala, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Björkholm
authors.affiliation: Interdisciplinary Center for Neurosciences, Heidelberg University, Heidelberg 69120, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hellwig
authors.affiliation: Heidelberg University Biochemistry Center (BZH), 69120 Heidelberg, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Himmels
authors.affiliation: Heidelberg University Biochemistry Center (BZH), 69120 Heidelberg, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ruiz de Almodóvar
authors.affiliation: Heidelberg University Biochemistry Center (BZH), 69120 Heidelberg, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Brügger
authors.affiliation: Heidelberg University Biochemistry Center (BZH), 69120 Heidelberg, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Wieland
authors.affiliation: Heidelberg University Biochemistry Center (BZH), 69120 Heidelberg, Germany.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Ernst
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D019556:COS Cells; D002448:Cell Adhesion / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000378:metabolism*; D003571:Cytochalasin B / Q000494:pharmacology*; D029043:Ebolavirus / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D005434:Flow Cytometry; D057809:HEK293 Cells; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018613:Microscopy, Confocal; D017434:Protein Structure, Tertiary; D019821:Simvastatin / Q000494:pharmacology*; D014760:Viral Fusion Proteins / Q000187:drug effects* / Q000378:metabolism; D037521:Virulence Factors / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000494:pharmacology*
chemical_list: D000924:Anticholesteremic Agents; D014760:Viral Fusion Proteins; D037521:Virulence Factors; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D003571:Cytochalasin B; D002784:Cholesterol; D019821:Simvastatin