Ebola Virus Delta Peptide Is an Enterotoxin

Abstract

During the 2013-2016 West African 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). Here, the murine ligated ileal loop model was used to demonstrate that delta peptide is a potent enterotoxin. Dramatic intestinal fluid secretion followed injection of biologically relevant amounts of delta peptide into ileal loops, along with gross destruction of villous architecture and loss of goblet cell polysaccharides. Transcriptomic analyses showed that delta peptide triggers damage response and cell survival pathways. It also downregulates the expression of transporters and exchangers that mediate absorption of ions, sugars, and small chain fatty acids. Delta peptide induces fluid secretion through pathways that include the ANO1 calcium-activated chloride channel, and prostaglandin signaling. Delta peptide may contribute to EBOV-induced gastrointestinal pathology in humans and presents a potential therapeutic target.