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Effects of Ebola virus glycoproteins on endothelial cell activation and barrier function.
- Source :
-
Journal of virology [J Virol] 2005 Aug; Vol. 79 (16), pp. 10442-50. - Publication Year :
- 2005
-
Abstract
- Ebola virus causes severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. Vascular instability and dysregulation are disease-decisive symptoms during severe infection. While the transmembrane glycoprotein GP(1,2) has been shown to cause endothelial cell destruction, the role of the soluble glycoproteins in pathogenesis is largely unknown; however, they are hypothesized to be of biological relevance in terms of target cell activation and/or increase of endothelial permeability. Here we show that virus-like particles (VLPs) consisting of the Ebola virus matrix protein VP40 and GP(1,2) were able to activate endothelial cells and induce a decrease in barrier function as determined by impedance spectroscopy and hydraulic conductivity measurements. In contrast, the soluble glycoproteins sGP and delta-peptide did not activate endothelial cells or change the endothelial barrier function. The VLP-induced decrease in barrier function was further enhanced by the cytokine tumor necrosis factor alpha (TNF-alpha), which is known to induce a long-lasting decrease in endothelial cell barrier function and is hypothesized to play a key role in Ebola virus pathogenesis. Surprisingly, sGP, but not delta-peptide, induced a recovery of endothelial barrier function following treatment with TNF-alpha. Our results demonstrate that Ebola virus GP(1,2) in its particle-associated form mediates endothelial cell activation and a decrease in endothelial cell barrier function. Furthermore, sGP, the major soluble glycoprotein of Ebola virus, seems to possess an anti-inflammatory role by protecting the endothelial cell barrier function.
- Subjects :
- Cells, Cultured
E-Selectin genetics
Humans
Intercellular Adhesion Molecule-1 genetics
RNA, Messenger analysis
Tumor Necrosis Factor-alpha pharmacology
Vascular Cell Adhesion Molecule-1 genetics
Virion physiology
Ebolavirus physiology
Endothelial Cells metabolism
Glycoproteins physiology
Viral Nonstructural Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-538X
- Volume :
- 79
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 16051836
- Full Text :
- https://doi.org/10.1128/JVI.79.16.10442-10450.2005