Ebola virus delta peptide is an enterotoxin

Lilia I. Melnik, Shantanu Guha, Jenisha Ghimire, Allison R. Smither, Brandon J. Beddingfield, Andrew R. Hoffmann, Leisheng Sun, Nathan A. Ungerleider, Melody C. Baddoo, Erik K. Flemington, William R. Gallaher, William C. Wimley, Robert F. Garry

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number110172
JournalCell Reports
Volume38
Issue number1
DOIs
StatePublished - Jan 4 2022

Keywords

  • Ebola virus
  • Ebola virus disease gastrointestinal pathology
  • cell damage response
  • cell membrane transport and exchange
  • cell survival pathways
  • cellular fluid excretion
  • delta peptide
  • enterotoxin
  • transcriptomic analysis

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

Fingerprint

Dive into the research topics of 'Ebola virus delta peptide is an enterotoxin'. Together they form a unique fingerprint.

Cite this