title: Phosphorylation of Marburg virus matrix protein VP40 triggers assembly of nucleocapsids with the viral envelope at the plasma membrane.
abstract: Marburg virus (MARV) matrix protein VP40 plays a key role in virus assembly, recruiting nucleocapsids and the surface protein GP to filopodia, the sites of viral budding. In addition, VP40 is the only MARV protein able to induce the release of filamentous virus-like particles (VLPs) indicating its function in MARV budding. Here, we demonstrated that VP40 is phosphorylated and that tyrosine residues at positions 7, 10, 13 and 19 represent major phosphorylation acceptor sites. Mutagenesis of these tyrosine residues resulted in expression of a non-phosphorylatable form of VP40 (VP40(mut) ). VP40(mut)  was able to bind to cellular membranes, produce filamentous VLPs, and inhibit interferon-induced gene expression similarly to wild-type VP40. However, VP40(mut)  was specifically impaired in its ability to recruit nucleocapsid structures into filopodia, and released infectious VLPs (iVLPs) had low infectivity. These results indicated that tyrosine phosphorylation of VP40 is important for triggering the recruitment of nucleocapsids to the viral envelope.
authors: Institut für Virologie, Philipps-Universität Marburg, Hans Meerwein-Str. 2, 35043 Marburg, Germany.
authors: Larissa
authors: L
authors: Kolesnikova
authors: Eva
authors: E
authors: Mittler
authors: Gordian
authors: G
authors: Schudt
authors: Hosam
authors: H
authors: Shams-Eldin
authors: Stephan
authors: S
authors: Becker
mesh_terms: D019943:Amino Acid Substitution; D002460:Cell Line; D002462:Cell Membrane / Q000821:virology*; D006801:Humans; D029024:Marburgvirus / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D019251:Nucleocapsid / Q000378:metabolism*; D010766:Phosphorylation; D055503:Protein Multimerization; D014443:Tyrosine / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly
chemical_list: D050505:Mutant Proteins; C080981:VP40 protein, virus; D014763:Viral Matrix Proteins; D014443:Tyrosine