title: Ebola Virus Infections in Nonhuman Primates Are Temporally Influenced by Glycoprotein Poly-U Editing Site Populations in the Exposure Material.
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.
authors.affiliation: Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. john.c.trefry.ctr@mail.mil.
authors.forename: John C
authors.initials: JC
authors.lastname: Trefry
authors.affiliation: Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. suzanne.e.wollen.ctr@mail.mil.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Wollen
authors.affiliation: Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. farooq.nasar.ctr@mail.mil.
authors.forename: Farooq
authors.initials: F
authors.lastname: Nasar
authors.affiliation: Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. joshua.d.shamblin.civ@mail.mil.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Shamblin
authors.affiliation: Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. kern.steven0@gmail.com.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Kern
authors.affiliation: 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.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Bearss
authors.affiliation: 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.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Jefferson
authors.affiliation: 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.
authors.forename: Taylor B
authors.initials: TB
authors.lastname: Chance
authors.affiliation: 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.
authors.forename: Jeffery R
authors.initials: JR
authors.lastname: Kugelman
authors.affiliation: 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.
authors.forename: Jason T
authors.initials: JT
authors.lastname: Ladner
authors.affiliation: Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. anna.honko@nih.gov.
authors.forename: Anna N
authors.initials: AN
authors.lastname: Honko
authors.affiliation: Battelle Memorial Institute, 505 King Ave., Columbus, OH 43201, USA. kobsd@battelle.org.
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Kobs
authors.affiliation: Battelle Memorial Institute, 505 King Ave., Columbus, OH 43201, USA. wendingm@battelle.org.
authors.forename: Morgan Q S
authors.initials: MQ
authors.lastname: Wending
authors.affiliation: Battelle Memorial Institute, 505 King Ave., Columbus, OH 43201, USA. SabourinC@battelle.org.
authors.forename: Carol L
authors.initials: CL
authors.lastname: Sabourin
authors.affiliation: Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. william.d.pratt.civ@mail.mil.
authors.forename: William D
authors.initials: WD
authors.lastname: Pratt
authors.affiliation: 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.
authors.forename: Gustavo F
authors.initials: GF
authors.lastname: Palacios
authors.affiliation: Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. margaret.l.pitt.civ@mail.mil.
authors.forename: M Louise M
authors.initials: ML
authors.lastname: Pitt
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019142:Hemorrhagic Fever, Ebola / Q000473:pathology* / Q000821:virology*; D007273:Injections, Intramuscular; D008252:Macaca fascicularis; D011072:Poly U / Q000032:analysis*; D016019:Survival Analysis; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism; D037521:Virulence Factors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D014759:Viral Envelope Proteins; D037521:Virulence Factors; C113189:envelope glycoprotein, Ebola virus; D011072:Poly U
keywords: Ebola virus; Kikwit; RNA editing; animal model; filovirus; glycoprotein; nonhuman primate; pathogenesis; therapeutic; vaccine