The multiple roles of sGP in Ebola pathogenesis

Abstract

Ebola causes severe hemorrhagic fever in humans and nonhuman primates, and there are currently no approved therapeutic countermeasures. The virulence of Ebola virus (EBOV) may be partially attributed to the secreted glycoprotein (sGP), which is the main product transcribed from its GP gene. sGP is secreted from infected cells and can be readily detected in the serum of EBOV-infected hosts. This review summarizes the multiple roles that sGP may play during infection and highlights the implications for the future design of vaccines and treatments.

FIG. 1.

The impact of secreted glycoprotein (sGP) in Ebola pathogenesis. Following the entry of Ebola into a target cell, the viral genome is released and transcriptional editing of the GP gene leads to the production of three proteins, sGP, GP_1,2, and ssGP (A). sGP is initially synthesized as pre-sGP, a trans-Golgi-specific precursor that undergoes proteolytic cleavage by cellular proteases, such as furin. This maturation leads to the formation of two monomers, sGP and Δ-peptide (B). sGP monomers then assemble as homodimers in the cytoplasm and are released into the extracellular medium. sGP is currently thought to serve as a decoy antigen (C), be involved in antigenic subversion (D), and play a role in restoring the barrier function of endothelial cells (E). Other proposed effects, such as neutrophil inactivation (F) and induction of apoptosis in bystander cells (G), are less established. sGP monomers were also shown to assemble as heterodimers with GP₂, suggesting a structural role for sGP (H); however, the mechanism behind this assembly is still unknown. The Δ-peptide is also secreted from Ebola-infected cells, but at a much slower rate, since it is retained in the cell for a longer period. Once in the extracellular medium, it was shown to be able to block the entry of filoviruses; however, the mechanism is yet to be elucidated (I). Color images available online at www.liebertpub.com/vim