Lipid raft microdomains: a gateway for compartmentalized trafficking of Ebola and Marburg viruses.
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.
Bavari
Sina
S
Dept. of Cell Biology and Biochemistry, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702-5011, USA. bavaris@ncifcrf.gov
Bosio
Catharine M
CM
Wiegand
Elizabeth
E
Ruthel
Gordon
G
Will
Amy B
AB
Geisbert
Thomas W
TW
Hevey
Michael
M
Schmaljohn
Connie
C
Schmaljohn
Alan
A
Aman
M Javad
MJ
D002478:Cells, Cultured; D029043:Ebolavirus / Q000502:physiology*; D005677:G(M1) Ganglioside / Q000378:metabolism; D006801:Humans; D029024:Marburgvirus / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D021962:Membrane Microdomains / Q000821:virology*; D014759:Viral Envelope Proteins / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000378:metabolism; D014771:Virion / Q000502:physiology; D019065:Virus Assembly
C081324:GP-protein, Marburg virus; D008562:Membrane Glycoproteins; C080981:VP40 protein, virus; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; C110614:transmembrane glycoprotein, Ebola virus; D005677:G(M1) Ganglioside