Tsg101 Is Recruited by a Late Domain of the Nucleocapsid Protein To Support Budding of Marburg Virus-Like Particles
Open Access
- 1 August 2010
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 84 (15), 7847-7856
- https://doi.org/10.1128/jvi.00476-10
Abstract
The nucleoprotein NP of Marburg virus (MARV) is the major component of the viral nucleocapsid, which also consists of the viral proteins VP35, L, and VP30, as well as the viral genome. During virus assembly at the plasma membrane, the nucleocapsids are enwrapped by the major matrix protein VP40 and the viral envelope, which contains the transmembrane glycoprotein GP. Upon recombinant expression, VP40 alone is able to induce the formation and release of virus-like particles (VLPs) that closely resemble the filamentous morphology of MARV particles. Release of these VP40-induced VLPs is partially dependent on the cellular ESCRT machinery, which interacts with a late-domain motif in VP40. Coexpression with NP significantly enhances the budding of VP40-induced VLPs by an unknown mechanism. In the present study we analyzed the impact of late domains present in NP on the release of VLPs. We observed that the ESCRT I protein Tsg101 was recruited by NP into NP-induced inclusions in the perinuclear region. In the presence of VP40, NP was then recruited to VP40-positive membrane clusters and, in turn, recruited Tsg101 via a C-terminal PSAP late-domain motif in NP. This PSAP motif also mediated a dramatically enhanced incorporation of Tsg101 into VLPs, and its deletion significantly diminished the positive effect of NP on the release of VLPs. Taken together, these data indicate that NP enhances budding of VLPs by recruiting Tsg101 to the VP40-positive budding site through a PSAP late-domain motif.Keywords
This publication has 30 references indexed in Scilit:
- Single-Injection Vaccine Protects Nonhuman Primates against Infection with Marburg Virus and Three Species of Ebola VirusJournal of Virology, 2009
- The Nucleocapsid Region of HIV-1 Gag Cooperates with the PTAP and LYPXnL Late Domains to Recruit the Cellular Machinery Necessary for Viral BuddingPLoS Pathogens, 2009
- Vacuolar Protein Sorting Pathway Contributes to the Release of Marburg VirusJournal of Virology, 2009
- In Vitro Budding of Intralumenal Vesicles into Late Endosomes Is Regulated by Alix and Tsg101Molecular Biology of the Cell, 2008
- Human Immunodeficiency Virus Type 1 Gag Engages the Bro1 Domain of ALIX/AIP1 through the NucleocapsidJournal of Virology, 2008
- Differential functions of Hrs and ESCRT proteins in endocytic membrane traffickingExperimental Cell Research, 2008
- Filoviruses: Interactions with the host cellCellular and Molecular Life Sciences, 2007
- Mechanisms for enveloped virus budding: Can some viruses do without an ESCRT?Virology, 2007
- Role of the Transmembrane Domain of Marburg Virus Surface Protein GP in Assembly of the Viral EnvelopeJournal of Virology, 2007
- Budding of Marburgvirus is associated with filopodiaCellular Microbiology, 2007