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

Viruses

John C. Trefry¹  Suzanne E. Wollen¹  Farooq Nasar¹  Joshua D. Shamblin¹  Steven J. Kern¹  Jeremy J. Bearss²  Michelle A. Jefferson²  Taylor B. Chance²  Jeffery R. Kugelman⁴  Jason T. Ladner⁴  Anna N. Honko¹  Dean J. Kobs³  Morgan Q.S. Wending³  Carol L. Sabourin³  William D. Pratt¹  Gustavo F. Palacios⁴  M. Louise M. Pitt¹ 

[1] Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA;Pathology Division, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA;Battelle Memorial Institute, 505 King Ave., Columbus, OH 43201, USA;Molecular and Translational Sciences, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA;

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

DOI  :  10.3390/v7122969

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.