Structural rearrangement of Ebola virus VP40 begets multiple functions in the virus life cycle

Bornholdt, Z.A., et al. Cell 154, 763-774 (2013)

Speaker: Jui-Chieh Yin (尹睿婕)                                         Time: 13:10~14:00, Oct.15, 2014

Commentator: Dr. Yu-Chih Lo (羅玉枝老師)                     Place: Room 601

Abstract

Ebolaviruses cause severe hemorrhagic fever in infected humans with high fatality rates. There is no proper therapeutics and vaccine nowadays. Ebolaviruses encode seven proteins, and the major viral matrix protein VP40 regulates assembly and budding of virus¹. Currently, the crystal structure of ebola virus VP40 has revealed that it is essential for regulation of viral transcription, virus trafficking to the membrane and, virus budding². Besides, VP40 grows multiple crystal forms which are critical to affect the viral life cycle. It can help ebola virus to assemble and trigger the budding of filamentous virus-like particles (VLPs). However, the mechanism and conformation of VP40-driven matrix assembly and budding remains unknown. To clarify the structure of VP40, the authors defined that VP40 forms a dimer and its dimeric interface is important to matrix assembly and viral budding. Furthermore, they used immunofluorescence analysis and transmission electron microscopy to reveal that how the viral matrix is assembled. They discovered that dimeric structure controls the trafficking to the plasma membrane and it further assemble end-to-end into filaments through interaction between C-terminal domains. The assembled filaments change electrostatic interactions at the plasma membrane and form hexamer. These hexamers further construct a multilayered structure that is influenced on VP40 assembly into the viral matrix. Alternatively, VP40 octameric ring reduces viral transcription. In conclusion, the authors identified differentrearrangements of VP40 which achieves its multiple functions during viral assembly or budding. This study provides insights into the development of new therapeutic strategies through blocking or destroying VP40 conformational change to prevent virus assembly and budding.

References

1.         Adu-Gyamfi, E., Digman, M.A., Gratton, E. & Stahelin, R.V. Investigation of Ebola VP40 assembly and oligomerization in live cells using number and brightness analysis. Biophysical journal 102, 2517-2525 (2012)

2.         Hoenen, T., et al. Oligomerization of Ebola virus VP40 is essential for particle morphogenesis and regulation of viral transcription. Journal of virology 84, 7053-7063 (2010)