title: Multivesicular bodies as a platform for formation of the Marburg virus envelope.
abstract: 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.
authors.affiliation: Institut für Virologie der Philipps-Universität Marburg, Robert-Koch-Strasse 17, D-35037 Marburg, Germany.
authors.forename: Larissa
authors.initials: L
authors.lastname: Kolesnikova
authors.forename: Beate
authors.initials: B
authors.lastname: Berghöfer
authors.forename: Sandra
authors.initials: S
authors.lastname: Bamberg
authors.forename: Stephan
authors.initials: S
authors.lastname: Becker
mesh_terms: D000818:Animals; D016537:Gangliosidosis, GM1 / Q000378:metabolism; D006801:Humans; D029024:Marburgvirus / Q000737:chemistry / Q000648:ultrastructure*; D008565:Membrane Proteins / Q000378:metabolism; D016253:Microscopy, Immunoelectron; D014759:Viral Envelope Proteins / Q000032:analysis / Q000502:physiology*; D014763:Viral Matrix Proteins / Q000032:analysis / Q000502:physiology*; D014771:Virion / Q000502:physiology
chemical_list: D008565:Membrane Proteins; C080981:VP40 protein, virus; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins