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J Virol. 2017 May 24. pii: JVI.00438-17. doi: 10.1128/JVI.00438-17. [Epub ahead of print]

Ebola Virus Delta Peptide is a Viroporin.

Author information

1
Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
2
Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
3
Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
4
Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
5
Department of Microbiology, Immunology and Parasitology, LSU Health, New Orleans LA 70112.
6
Mockingbird Nature Research Group, Pearl River, LA 70452, USA.
7
Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA wwimley@tulane.edu rfgarry@tulane.edu.
8
Zalgen Labs, LLC, Germantown, MD 20876, USA.
9
Tulane Center of Excellence, Global Viral Network.
10
Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA. wwimley@tulane.edu rfgarry@tulane.edu.

Abstract

The Ebola virus (EBOV) genome encodes for a partly conserved, 40-residue, nonstructural polypeptide, called the delta peptide, which is produced in abundance during Ebola virus disease. The function of the delta peptide is unknown, but sequence analysis has suggested that delta peptide could be a viroporin, belonging to a diverse family of membrane-permeabilizing small polypeptides involved in replication and pathogenesis of numerous viruses. Full length and conserved C-terminal delta peptide fragments permeabilize the plasma membranes of nucleated cells of rodent, dog, monkey and human origin, increase ion permeability across confluent cell monolayers and permeabilize synthetic lipid bilayers. Permeabilization activity is completely dependent on the disulfide bond between the two conserved cysteines. The conserved C-terminal portion of the peptide is biochemically stable in human serum, and most serum-stable fragments have full activity. Taken together, the evidence strongly suggests that Ebola virus delta peptide is a viroporin, and may be a novel, targetable aspect of Ebola virus disease pathology.Importance During the unparalleled West African outbreak of Ebola virus disease (EVD) that began in late 2013, the lack of effective countermeasures resulted in chains of serial infection and a high mortality rate among infected patients. A better understanding of disease pathology is desperately needed to develop better countermeasures. We show here that the Ebola virus delta peptide, a conserved non-structural protein produced in large quantities by infected cells, has the characteristics of a viroporin. This information suggests a critical role for the delta peptide in Ebola virus disease pathology, and a possible target for novel countermeasures.

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