title: Considerations in the Use of Nonhuman Primate Models of Ebola Virus and Marburg Virus Infection.
abstract: The filoviruses, Ebola virus and Marburg virus, are zoonotic pathogens that cause severe hemorrhagic fever in humans and nonhuman primates (NHPs), with case-fatality rates ranging from 23% to 90%. The current outbreak of Ebola virus infection in West Africa, with >26 000 cases, demonstrates the long-underestimated public health danger that filoviruses pose as natural human pathogens. Currently, there are no vaccines or treatments licensed for human use. Licensure of any medical countermeasure may require demonstration of efficacy in the gold standard cynomolgus or rhesus macaque models of filovirus infection. Substantial progress has been made over the last decade in characterizing the filovirus NHP models. However, there is considerable debate over a variety of experimental conditions, including differences among filovirus isolates used, routes and doses of exposure, and euthanasia criteria, all of which may contribute to variability of results among different laboratories. As an example of the importance of understanding these differences, recent data with Ebola virus shows that an addition of a single uridine residue in the glycoprotein gene at the editing site attenuates the virus. Here, we draw on decades of experience working with filovirus-infected NHPs to provide a perspective on the importance of various experimental conditions.
authors.affiliation: Galveston National Laboratory Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Geisbert
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada Department of Medical Microbiology Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada.
authors.forename: James E
authors.initials: JE
authors.lastname: Strong
authors.affiliation: Laboratory of Virology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
mesh_terms: D000354:Africa, Western / Q000453:epidemiology; D000818:Animals; D004195:Disease Models, Animal; D004196:Disease Outbreaks; D029043:Ebolavirus / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology; D019142:Hemorrhagic Fever, Ebola / Q000453:epidemiology* / Q000276:immunology* / Q000821:virology; D006801:Humans; D008252:Macaca fascicularis / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology; D008379:Marburg Virus Disease / Q000453:epidemiology* / Q000276:immunology* / Q000821:virology; D029024:Marburgvirus / Q000276:immunology*; D011323:Primates / Q000276:immunology / Q000821:virology*; D014613:Vaccines, Attenuated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D006023:Glycoproteins; D014613:Vaccines, Attenuated; D014765:Viral Vaccines
keywords: Ebola virus; Marburg virus; animal model; filovirus; nonhuman primate; treatment; vaccine