Format

Send to

Choose Destination
Viruses. 2015 Dec 19;7(12):6739-54. doi: 10.3390/v7122969.

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

Author information

1
Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. john.c.trefry.ctr@mail.mil.
2
Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. suzanne.e.wollen.ctr@mail.mil.
3
Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. farooq.nasar.ctr@mail.mil.
4
Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. joshua.d.shamblin.civ@mail.mil.
5
Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. kern.steven0@gmail.com.
6
Pathology Division, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. jeremy.j.bearss.mil@mail.mil.
7
Pathology Division, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. michelle.a.jefferson.mil@mail.mil.
8
Pathology Division, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. taylor.b.chance.mil@mail.mil.
9
Molecular and Translational Sciences, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. jeffery.r.kugelman.mil@mail.mil.
10
Molecular and Translational Sciences, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. jason.t.ladner.ctr@mail.mil.
11
Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. anna.honko@nih.gov.
12
Battelle Memorial Institute, 505 King Ave., Columbus, OH 43201, USA. kobsd@battelle.org.
13
Battelle Memorial Institute, 505 King Ave., Columbus, OH 43201, USA. wendingm@battelle.org.
14
Battelle Memorial Institute, 505 King Ave., Columbus, OH 43201, USA. SabourinC@battelle.org.
15
Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. william.d.pratt.civ@mail.mil.
16
Molecular and Translational Sciences, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. gustavo.f.palacios.ctr@mail.mil.
17
Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. margaret.l.pitt.civ@mail.mil.

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.

KEYWORDS:

Ebola virus; Kikwit; RNA editing; animal model; filovirus; glycoprotein; nonhuman primate; pathogenesis; therapeutic; vaccine

PMID:
26703716
PMCID:
PMC4690892
DOI:
10.3390/v7122969
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center