Vacuolar protein sorting pathway contributes to the release of marburg virus

Larissa Kolesnikova, Thomas Strecker, Eiji Morita, Florian Zielecki, Eva Mittler, Colin Crump, Stephan Becker

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35 Scopus citations

Abstract

VP40, the major matrix protein of Marburg virus, is the main driving force for viral budding. Additionally, cellular factors are likely to play an important role in the release of progeny virus. In the present study, we characterized the influence of the vacuolar protein sorting (VPS) pathway on the release of virus-like particles (VLPs), which are induced by Marburg virus VP40. In the supernatants of HEK 293 cells expressing VP40, different populations of VLPs with either a vesicular or a filamentous morphology were detected. While the filaments were almost completely composed of VP40, the vesicular particles additionally contained considerable amounts of cellular proteins. In contrast to that in the vesicles, the VP40 in the filaments was regularly organized, probably inducing the elimination of cellular proteins from the released VLPs. Vesicular particles were observed in the supernatants of cells even in the absence of VP40. Mutation of the late-domain motif in VP40 resulted in reduced release of filamentous particles, and likewise, inhibition of the VPS pathway by expression of a dominant-negative (DN) form of VPS4 inhibited the release of filamentous particles. In contrast, the release of vesicular particles did not respond significantly to the expression of DN VPS4. Like the budding of VLPs, the budding of Marburg virus particles was partially inhibited by the expression of DN VPS4. While the release of VLPs from VP40-expressing cells is a valuable tool with which to investigate the budding of Marburg virus particles, it is important to separate filamentous VLPs from vesicular particles, which contain many cellular proteins and use a different budding mechanism.

Original languageEnglish (US)
Pages (from-to)2327-2337
Number of pages11
JournalJournal of virology
Volume83
Issue number5
DOIs
StatePublished - Mar 1 2009
Externally publishedYes

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Kolesnikova, L., Strecker, T., Morita, E., Zielecki, F., Mittler, E., Crump, C., & Becker, S. (2009). Vacuolar protein sorting pathway contributes to the release of marburg virus. Journal of virology, 83(5), 2327-2337. https://doi.org/10.1128/JVI.02184-08