Ebola virus delta peptide is an enterotoxin

Authors

• Lilia I. Melnik, Tulane University School of Medicine, New Orleans, LA
• Shantanu Guha, Tulane University School of Medicine, New Orleans, LA
• Jenisha Ghimire, Tulane University School of Medicine, New Orleans, LA
• Allison R. Smither, Tulane University School of Medicine, New Orleans, LA
• Brandon J. Beddingfield, Tulane University School of Medicine, New Orleans, LA
• Andrew R. Hoffmann, Tulane University School of Medicine, New Orleans, LA
• Leisheng Sun, Tulane University School of Medicine, New Orleans, LA
• Nathan A. Ungerleider, Tulane University, New Orleans, LA
• Melody C. Baddoo, Tulane University, New Orleans, LA
• Erik K. Flemington, Tulane University, New Orleans, LA
• William R. Gallaher, LSU Health Sciences Center - New Orleans
• William C. Wimley, Tulane University School of Medicine, New Orleans, LA
• Robert F. Garry, Tulane University School of Medicine, New Orleans, LA

Document Type

Article

Publication Date

1-4-2022

Publication Title

Cell Reports

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.

PubMed ID

34986351

Volume

38

Issue

1

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Melnik, Lilia I.; Guha, Shantanu; Ghimire, Jenisha; Smither, Allison R.; Beddingfield, Brandon J.; Hoffmann, Andrew R.; Sun, Leisheng; Ungerleider, Nathan A.; Baddoo, Melody C.; Flemington, Erik K.; Gallaher, William R.; Wimley, William C.; and Garry, Robert F., "Ebola virus delta peptide is an enterotoxin" (2022). School of Graduate Studies Faculty Publications. 579.
https://digitalscholar.lsuhsc.edu/sogs_facpubs/579
10.1016/j.celrep.2021.110172