Spatiotemporal aspects of filovirus entry and release are poorly understood. Lipid rafts act as functional platforms for multiple cellular signaling and trafficking processes. Here, we report the compartmentalization of Ebola and Marburg viral proteins within lipid rafts during viral assembly and budding. Filoviruses released from infected cells incorporated raft-associated molecules, suggesting that viral exit occurs at the rafts. Ectopic expression of Ebola matrix protein and glycoprotein supported raft-dependent release of filamentous, virus-like particles (VLPs), strikingly similar to live virus as revealed by electron microscopy. Our findings also revealed that the entry of filoviruses requires functional rafts, identifying rafts as the site of virus attack. The identification of rafts as the gateway for the entry and exit of filoviruses and raft-dependent generation of VLPs have important implications for development of therapeutics and vaccination strategies against infections with Ebola and Marburg viruses.
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4 March 2002
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March 04 2002
Lipid Raft Microdomains : A Gateway for Compartmentalized Trafficking of Ebola and Marburg Viruses
Sina Bavari,
Sina Bavari
1U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702
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Catharine M. Bosio,
Catharine M. Bosio
1U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702
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Elizabeth Wiegand,
Elizabeth Wiegand
1U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702
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Gordon Ruthel,
Gordon Ruthel
1U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702
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Amy B. Will,
Amy B. Will
1U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702
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Thomas W. Geisbert,
Thomas W. Geisbert
1U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702
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Michael Hevey,
Michael Hevey
1U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702
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Connie Schmaljohn,
Connie Schmaljohn
1U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702
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Alan Schmaljohn,
Alan Schmaljohn
1U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702
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M. Javad Aman
M. Javad Aman
1U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702
2Clinical Research Management Inc., Frederick, MD 21702
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Sina Bavari
1U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702
Catharine M. Bosio
1U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702
Elizabeth Wiegand
1U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702
Gordon Ruthel
1U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702
Amy B. Will
1U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702
Thomas W. Geisbert
1U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702
Michael Hevey
1U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702
Connie Schmaljohn
1U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702
Alan Schmaljohn
1U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702
M. Javad Aman
1U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702
2Clinical Research Management Inc., Frederick, MD 21702
Address correspondence to M. Javad Aman or Sina Bavari, Dept. of Cell Biology and Biochemistry, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Frederick, MD 21702-5011. Phone: 301-619-6727/301-619-4246; Fax: 301-619-2348; E-mail: [email protected] or [email protected]
*
Abbreviations used in this paper: GP, glycoprotein; GPI, glycosylphosphatidylinositol; TrfR, transferrin receptor; VLP, virus-like particle.
Received:
August 29 2001
Revision Received:
December 07 2001
Accepted:
January 24 2002
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2002
J Exp Med (2002) 195 (5): 593–602.
Article history
Received:
August 29 2001
Revision Received:
December 07 2001
Accepted:
January 24 2002
Citation
Sina Bavari, Catharine M. Bosio, Elizabeth Wiegand, Gordon Ruthel, Amy B. Will, Thomas W. Geisbert, Michael Hevey, Connie Schmaljohn, Alan Schmaljohn, M. Javad Aman; Lipid Raft Microdomains : A Gateway for Compartmentalized Trafficking of Ebola and Marburg Viruses. J Exp Med 4 March 2002; 195 (5): 593–602. doi: https://doi.org/10.1084/jem.20011500
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