The Delta Peptide of Ebola Virus has Potent Viroporin Activity

Abstract

The Delta peptide, cleaved from the soluble glycoprotein (sGP) of Ebola virus (EBOV), is a partially conserved, 40-residue nonstructural polypeptide that has no known function. This peptide shows high similarity in amino acid composition to membrane permeabilizing peptides, including a peptide in the diarrhea-inducing viroporin, NSP4, of Rotavirus. In addition, EBOV disease (EVD) survivors from West Africa have antibodies against the Delta peptide. Therefore, we hypothesize that the Delta peptide has an important role as a viroporin in EVD pathology. Here we show that a peptide corresponding to the serum-stable, conserved C-terminal sequence of Delta peptide permeabilizes and kills nucleated mammalian cells, and potently increasing ion permeability across synthetic lipid bilayers. Importantly, this permeabilizing activity is eliminated by the reduction of the disulfide bond between conserved cysteines. We conclude that EBOV Delta peptide does not form large unregulated pores through membranes, but rather increases ionic permeation, which is similar to other viroporins. By this mechanism, it could contribute to EVD pathology in human through vascular leakage, enterotoxic effects, or other cytotoxic pathways.