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Journal of Virology, November 2004, p. 12277-12287, Vol. 78, No. 22
0022-538X/04/$08.00+0 DOI: 10.1128/JVI.78.22.12277-12287.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Multivesicular Bodies as a Platform for Formation of the Marburg Virus Envelope
Larissa Kolesnikova,
Beate Berghöfer,
Sandra Bamberg, and
Stephan Becker*
Institut für Virologie der Philips-Universität Marburg, Marburg, Germany
Received 29 April 2004/
Accepted 30 June 2004
The Marburg virus (MARV) envelope consists of a lipid membrane and two major proteins, the matrix protein VP40 and the glycoprotein GP. Both proteins use different intracellular transport pathways: GP utilizes the exocytotic pathway, while VP40 is transported through the retrograde late endosomal pathway. It is currently unknown where the proteins combine to form the viral envelope. In the present study, we identified the intracellular site where the two major envelope proteins of MARV come together as peripheral multivesicular bodies (MVBs). Upon coexpression with VP40, GP is redistributed from the trans-Golgi network into the VP40-containing MVBs. Ultrastructural analysis of MVBs suggested that they provide the platform for the formation of membrane structures that bud as virus-like particles from the cell surface. The virus-like particles contain both VP40 and GP. Single expression of GP also resulted in the release of particles, which are round or pleomorphic. Single expression of VP40 led to the release of filamentous structures that closely resemble viral particles and contain traces of endosomal marker proteins. This finding indicated a central role of VP40 in the formation of the filamentous structure of MARV particles, which is similar to the role of the related Ebola virusVP40. In MARV-infected cells, VP40 and GP are colocalized in peripheral MVBs as well. Moreover, intracellular budding of progeny virions into MVBs was frequently detected. Taken together, these results demonstrate an intracellular intersection between GP and VP40 pathways and suggest a crucial role of the late endosomal compartment for the formation of the viral envelope.
* Corresponding author. Mailing address: Institut für Virologie der Philipps-Universität Marburg, Robert-Koch-Strasse 17, D-35037 Marburg, Germany. Phone: 6421-2865433. Fax: 6421-2865482. E-mail: becker{at}staff.uni-marburg.de.
Journal of Virology, November 2004, p. 12277-12287, Vol. 78, No. 22
0022-538X/04/$08.00+0 DOI: 10.1128/JVI.78.22.12277-12287.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
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Copyright © 2004 by the American Society for Microbiology. All rights reserved.