This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wahl-Jensen, V. M.
Right arrow Articles by Schnittler, H.-J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wahl-Jensen, V. M.
Right arrow Articles by Schnittler, H.-J.

 Previous Article  |  Next Article 

Journal of Virology, August 2005, p. 10442-10450, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10442-10450.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Effects of Ebola Virus Glycoproteins on Endothelial Cell Activation and Barrier Function

Victoria M. Wahl-Jensen,1,2,{dagger} Tatiana A. Afanasieva,3,{dagger} Jochen Seebach,3 Ute Ströher,1,2 Heinz Feldmann,1,2 and Hans-Joachim Schnittler3*

Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada,1 Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada,2 Institut für Physiologie, Technische Universität, Dresden 01307, Germany3

Received 25 October 2004/ Accepted 1 May 2005

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 GP1,2 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 GP1,2 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 GP1,2 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.

* Corresponding author. Mailing address: Institut für Physiologie, Technische Universität, Medizinische Fakultät, Fetcherstraße 74, Dresden D-01307, Germany. Phone: 49-351-458 6007. Fax: 49-351-458 6301. E-mail: hans.schnittler{at}mailbox.tu-dresden.de.

{dagger} V.M.W.-J. and T.A.A. contributed equally to this work.

Journal of Virology, August 2005, p. 10442-10450, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10442-10450.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Krautkramer, E., Zeier, M. (2008). Hantavirus Causing Hemorrhagic Fever with Renal Syndrome Enters from the Apical Surface and Requires Decay-Accelerating Factor (DAF/CD55). J. Virol. 82: 4257-4264 [Abstract] [Full Text]  
  • Wahl-Jensen, V., Chapman, J., Asher, L., Fisher, R., Zimmerman, M., Larsen, T., Hooper, J. W. (2007). Temporal Analysis of Andes Virus and Sin Nombre Virus Infections of Syrian Hamsters. J. Virol. 81: 7449-7462 [Abstract] [Full Text]  
  • Shimojima, M., Takada, A., Ebihara, H., Neumann, G., Fujioka, K., Irimura, T., Jones, S., Feldmann, H., Kawaoka, Y. (2006). Tyro3 family-mediated cell entry of ebola and marburg viruses.. J. Virol. 80: 10109-10116 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»