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Journal of Virology, February 2005, p. 2413-2419, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.2413-2419.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Role of Ebola Virus Secreted Glycoproteins and Virus-Like Particles in Activation of Human Macrophages

Victoria Wahl-Jensen,1,2 Sabine K. Kurz,3 Paul R. Hazelton,2 Hans-Joachim Schnittler,4 Ute Ströher,1,2 Dennis R. Burton,3 and Heinz Feldmann1,2*

Special Pathogens Program, National Microbiology Laboratory,1 Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada,2 Department of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, California,3 Medizinische Fakultät, Institut für Physiologie, Dresden, Germany4

Received 27 April 2004/ Accepted 5 October 2004

Ebola virus, a member of the family Filoviridae, causes one of the most severe forms of viral hemorrhagic fever. In the terminal stages of disease, symptoms progress to hypotension, coagulation disorders, and hemorrhages, and there is prominent involvement of the mononuclear phagocytic and reticuloendothelial systems. Cells of the mononuclear phagocytic system are primary target cells and producers of inflammatory mediators. Ebola virus efficiently produces four soluble glycoproteins during infection: sGP, delta peptide ({Delta}-peptide), GP1, and GP1,2{Delta}. While the presence of these glycoproteins has been confirmed in blood (sGP) and in vitro systems, it is hypothesized that they are of biological relevance in pathogenesis, particularly target cell activation. To gain insight into their function, we expressed the four soluble glycoproteins in mammalian cells and purified and characterized them. The role of the transmembrane glycoprotein in the context of virus-like particles was also investigated. Primary human macrophages were treated with glycoproteins and virus-like particles and subsequently tested for activation by detection of several critical proinflammatory cytokines (tumor necrosis factor alpha, interleukin-6 [IL-6], and IL-1 beta) and the chemokine IL-8. The presentation of the glycoprotein was determined to be critical since virus-like particles, but not soluble glycoproteins, induced high levels of activation. We propose that the presentation of GP1,2 in the rigid form such as that observed on the surface of particles is critical for initiating a sufficient signal for the activation of primary target cells. The secreted glycoproteins do not appear to play any role in exogenous activation of these cells during Ebola virus infection.

* Corresponding author. Mailing address: Canadian Science Centre for Human and Animal Health, 1015 Arlington St., Winnipeg, Manitoba, R3E 3R2 Canada. Phone: (204) 789-6019. Fax: (204) 789-2140. E-mail: heinz_feldmann{at}hc-sc.gc.ca.

Journal of Virology, February 2005, p. 2413-2419, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.2413-2419.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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