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Viruses 2015, 7(12), 6739-6754; doi:10.3390/v7122969

Ebola Virus Infections in Nonhuman Primates Are Temporally Influenced by Glycoprotein Poly-U Editing Site Populations in the Exposure Material

1
Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA
2
Pathology Division, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA
3
Molecular and Translational Sciences, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA
4
Battelle Memorial Institute, 505 King Ave., Columbus, OH 43201, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Jens H. Kuhn
Received: 20 July 2015 / Revised: 3 December 2015 / Accepted: 7 December 2015 / Published: 19 December 2015
(This article belongs to the Collection Advances in Ebolavirus, Marburgvirus, and Cuevavirus Research)
View Full-Text   |   Download PDF [1481 KB, uploaded 19 December 2015]   |  

Abstract

Recent experimentation with the variants of the Ebola virus that differ in the glycoprotein’s poly-uridine site, which dictates the form of glycoprotein produced through a transcriptional stutter, has resulted in questions regarding the pathogenicity and lethality of the stocks used to develop products currently undergoing human clinical trials to combat the disease. In order to address these concerns and prevent the delay of these critical research programs, we designed an experiment that permitted us to intramuscularly challenge statistically significant numbers of naïve and vaccinated cynomolgus macaques with either a 7U or 8U variant of the Ebola virus, Kikwit isolate. In naïve animals, no difference in survivorship was observed; however, there was a significant delay in the disease course between the two groups. Significant differences were also observed in time-of-fever, serum chemistry, and hematology. In vaccinated animals, there was no statistical difference in survivorship between either challenge groups, with two succumbing in the 7U group compared to 1 in the 8U challenge group. In summary, survivorship was not affected, but the Ebola virus disease course in nonhuman primates is temporally influenced by glycoprotein poly-U editing site populations. View Full-Text
Keywords: Ebola virus; Kikwit; filovirus; nonhuman primate; glycoprotein; RNA editing; pathogenesis; animal model; vaccine; therapeutic Ebola virus; Kikwit; filovirus; nonhuman primate; glycoprotein; RNA editing; pathogenesis; animal model; vaccine; therapeutic
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Trefry, J.C.; Wollen, S.E.; Nasar, F.; Shamblin, J.D.; Kern, S.J.; Bearss, J.J.; Jefferson, M.A.; Chance, T.B.; Kugelman, J.R.; Ladner, J.T.; Honko, A.N.; Kobs, D.J.; Wending, M.Q.; Sabourin, C.L.; Pratt, W.D.; Palacios, G.F.; Pitt, M.L.M. Ebola Virus Infections in Nonhuman Primates Are Temporally Influenced by Glycoprotein Poly-U Editing Site Populations in the Exposure Material. Viruses 2015, 7, 6739-6754.

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