Ebola virus delta peptide is an enterotoxin.

During the 2013–2016 West African (WA) Ebola virus (EBOV) outbreak, severe gastrointestinal symptoms were common in patients and associated with poor outcome. Delta peptide is a conserved product of post-translational processing of the abundant EBOV soluble glycoprotein (sGP). The murine ligated ileal loop model was used to demonstrate that delta peptide is a potent enterotoxin. Dramatic intestinal fluid accumulation follows injection of biologically relevant amounts of delta peptide into ileal loops, along with gross alteration of villous architecture and loss of goblet cells. Transcriptomic analyses show that delta peptide triggers damage response and cell survival pathways and downregulates expression of transporters and exchangers. Induction of diarrhea by delta peptide occurs via cellular damage and regulation of genes that encode proteins involved in fluid secretion. While distinct differences exist between the ileal loop murine model and EBOV infection in humans, these results suggest that delta peptide may contribute to EBOV-induced gastrointestinal pathology. [Display omitted] • Delta peptide is a potent enterotoxin • Injection of delta peptide into murine ileal loops induces fluid accumulation • Delta peptide downregulates the expression of ion transporters and other exchangers • Delta peptide may present a potential therapeutic target Melnik et al. use the murine ligated ileal loop model to demonstrate that delta peptide is a potent enterotoxin. Intestinal fluid accumulation, alteration of villous architecture, and loss of goblet cells follow injection of delta peptide. Delta peptide induces diarrhea via direct cellular damage and regulation of fluid secretion. [ABSTRACT FROM AUTHOR]