Ebola glycoprotein (GP) is the only virus protein expressed on the surface of Ebola virus and mediates entry into target cells. However, several studies report that GP expression also causes cytotoxicity, although the underlying mechanism remains unknown. GP is also believed to be a key determinant of Ebola pathogenesis and virus-like particles (VLPs) containing GP are shown to activate human endothelial cells and macrophages. The other virus proteins tested were not cytotoxic. Collectively, these reports indicate that Ebola GP imparts cell rounding and cytotoxicity in addition to facilitating virus entry. As full-length GP but not the secreted form (sGP) is shown to cause cytotoxicity, this suggests that the release of sGP during Ebola virus infection could be a mechanism used by the virus to prevent cytotoxicity and replicate and spread throughout the body.
Ebola glycoprotein accumulates in the endoplasmic reticulum. Virology Journal 2011, 8:11 doi:10.1186/1743-422X-8-11
The Filoviridae family comprises of Ebola and Marburg viruses, which are known to cause lethal hemorrhagic fever. However, there is no effective anti-viral therapy or licensed vaccines currently available for these human pathogens. The envelope glycoprotein (GP) of Ebola virus, which mediates entry into target cells, is cytotoxic and this effect maps to a highly glycosylated mucin-like region in the surface subunit of GP (GP1). However, the mechanism underlying this cytotoxic property of GP is unknown. To gain insight into the basis of this GP-induced cytotoxicity, HEK293T cells were transiently transfected with full-length and mucin-deleted (Δmucin) Ebola GP plasmids and GP localization was examined relative to the nucleus, endoplasmic reticulum (ER), Golgi, early and late endosomes using deconvolution fluorescent microscopy. Full-length Ebola GP was observed to accumulate in the ER. In contrast, GPΔmucin was uniformly expressed throughout the cell and did not localize in the ER. The Ebola major matrix protein VP40 was also co-expressed with GP to investigate its influence on GP localization. GP and VP40 co- expression did not alter GP localization to the ER. Also, when VP40 was co-expressed with the nucleoprotein (NP), it localized to the plasma membrane while NP accumulated in distinct cytoplasmic structures lined with vimentin. These latter structures are consistent with aggresomes and may serve as assembly sites for filoviral nucleocapsids. Collectively, these data suggest that full-length GP, but not GPΔmucin, accumulates in the ER in close proximity to the nuclear membrane, which may underscore its cytotoxic property.