{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:42:14Z","timestamp":1789051334993,"version":"build-2803163510"},"reference-count":23,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T00:00:00Z","timestamp":1594684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Ongoing Ebola virus disease outbreaks in the Democratic Republic of the Congo follow the largest recorded outbreak in Western Africa (2013\u20132016). To combat outbreaks, testing of medical countermeasures (therapeutics or vaccines) requires a well-defined, reproducible, animal model. Here we present Ebola virus disease kinetics in 24 Chinese-origin rhesus monkeys exposed intramuscularly to a highly characterized, commercially available Kikwit Ebola virus Filovirus Animal Non-Clinical Group (FANG) stock. Until reaching predetermined clinical disease endpoint criteria, six animals underwent anesthesia for repeated clinical sampling and were compared to six that did not. Groups of three animals were euthanized and necropsied on days 3, 4, 5, and 6 post-exposure, respectively. In addition, three uninfected animals served as controls. Here, we present detailed characterization of clinical and laboratory disease kinetics and complete blood counts, serum chemistries, Ebola virus titers, and disease kinetics for future medical countermeasure (MCM) study design and control data. We measured no statistical difference in hematology, chemistry values, or time to clinical endpoint in animals that were anesthetized for clinical sampling during the acute disease compared to those that were not.<\/jats:p>","DOI":"10.3390\/v12070753","type":"journal-article","created":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T09:30:49Z","timestamp":1594719049000},"page":"753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Kikwit Ebola Virus Disease Progression in the Rhesus Monkey Animal Model"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7227-4831","authenticated-orcid":false,"given":"Richard S.","family":"Bennett","sequence":"first","affiliation":[{"name":"Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Frederick, MD 27102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7410-9741","authenticated-orcid":false,"given":"James","family":"Logue","sequence":"additional","affiliation":[{"name":"Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Frederick, MD 27102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David X.","family":"Liu","sequence":"additional","affiliation":[{"name":"Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Frederick, MD 27102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J.","family":"Reeder","sequence":"additional","affiliation":[{"name":"Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Frederick, MD 27102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisztina B.","family":"Janosko","sequence":"additional","affiliation":[{"name":"Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Frederick, MD 27102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna L.","family":"Perry","sequence":"additional","affiliation":[{"name":"Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Frederick, MD 27102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy K.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Frederick, MD 27102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Byrum","sequence":"additional","affiliation":[{"name":"Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Frederick, MD 27102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny","family":"Ragland","sequence":"additional","affiliation":[{"name":"Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Frederick, MD 27102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"St. Claire","sequence":"additional","affiliation":[{"name":"Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Frederick, MD 27102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6906-4403","authenticated-orcid":false,"given":"Ricky","family":"Adams","sequence":"additional","affiliation":[{"name":"Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Frederick, MD 27102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey L.","family":"Burdette","sequence":"additional","affiliation":[{"name":"Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Frederick, MD 27102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler M.","family":"Brady","sequence":"additional","affiliation":[{"name":"Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Frederick, MD 27102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyra","family":"Hadley","sequence":"additional","affiliation":[{"name":"Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Frederick, MD 27102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Colin","family":"Waters","sequence":"additional","affiliation":[{"name":"Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Frederick, MD 27102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Shim","sequence":"additional","affiliation":[{"name":"Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Frederick, MD 27102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Dowling","sequence":"additional","affiliation":[{"name":"Research Resources Section, Office of Biodefense, Research Resources, and Translational Research\/Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5601 Fishers Lane, Rockville, MD 20892-9825, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Qin","sequence":"additional","affiliation":[{"name":"Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5601 Fishers Lane, Rockville, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Crozier","sequence":"additional","affiliation":[{"name":"Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD 21702 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter B.","family":"Jahrling","sequence":"additional","affiliation":[{"name":"Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Frederick, MD 27102, USA"},{"name":"Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa E.","family":"Hensley","sequence":"additional","affiliation":[{"name":"Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Frederick, MD 27102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,14]]},"reference":[{"key":"ref_1","unstructured":"Howley, P.M., Knipe, D.M., and Whelan, S.P.J. (2020). Filoviridae. Fields Virology, Wolters Lluwer\/Lippincott Williams & Wilkins. [7th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1086\/515386","article-title":"A mouse model for evaluation of prophylaxis and therapy of Ebola hemorrhagic fever","volume":"178","author":"Bray","year":"1998","journal-title":"J. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chan, M., Leung, A., Griffin, B.D., Vandramelli, R., Tailor, N., Tierney, K., Audet, J., and Kobasa, D. (2019). Generation and Characterization of a Mouse-Adapted Makona Variant of Ebola Virus. Viruses, 11.","DOI":"10.3390\/v11110987"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1053\/jcpa.2001.0502","article-title":"Pathogenesis of experimental Ebola Zaire virus infection in BALB\/c mice","volume":"125","author":"Gibb","year":"2001","journal-title":"J. Comp. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"s453","DOI":"10.1093\/infdis\/jiy208","article-title":"Ebola Virus Infection in Commonly Used Laboratory Mouse Strains","volume":"218","author":"Haddock","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1053\/jcpa.2001.0503","article-title":"Haematological, biochemical and coagulation changes in mice, guinea-pigs and monkeys infected with a mouse-adapted variant of Ebola Zaire virus","volume":"125","author":"Bray","year":"2001","journal-title":"J. Comp. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"s203","DOI":"10.1086\/514305","article-title":"Pathogenesis of experimental Ebola virus infection in guinea pigs","volume":"179","author":"Connolly","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1177\/0300985814535612","article-title":"Experimental aerosolized guinea pig-adapted Zaire ebolavirus (variant: Mayinga) causes lethal pneumonia in guinea pigs","volume":"52","author":"Twenhafel","year":"2015","journal-title":"Vet. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1128\/JVI.02836-14","article-title":"Ebola virus transmission in guinea pigs","volume":"89","author":"Wong","year":"2015","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1093\/infdis\/jiv538","article-title":"Humanized Mouse Model of Ebola Virus Disease Mimics the Immune Responses in Human Disease","volume":"213","author":"Bird","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_11","first-page":"21","article-title":"Comparative pathogenesis of Ebola virus and Reston virus infection in humanized mice","volume":"4","author":"Ruibal","year":"2019","journal-title":"JCI Insight"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1093\/infdis\/jiw209","article-title":"The Domestic Ferret (Mustela putorius furo) as a Lethal Infection Model. for 3 Species of Ebolavirus","volume":"214","author":"Cross","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_13","first-page":"5","article-title":"Modeling Ebola Virus Transmission Using Ferrets","volume":"3","author":"Soule","year":"2018","journal-title":"Msphere"},{"key":"ref_14","first-page":"s466","article-title":"The Makona Variant of Ebola Virus Is Highly Lethal to Immunocompromised Mice and Immunocompetent Ferrets","volume":"218","author":"Wong","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/0035-9203(78)90058-5","article-title":"Ebola haemorrhagic fever: Experimental infection of monkeys","volume":"72","author":"Bowen","year":"1978","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"s991","DOI":"10.1093\/infdis\/jir336","article-title":"Host response dynamics following lethal infection of rhesus macaques with Zaire ebolavirus","volume":"204","author":"Ebihara","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1016\/S0002-9440(10)63591-2","article-title":"Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: Evidence that dendritic cells are early and sustained targets of infection","volume":"163","author":"Geisbert","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"503","DOI":"10.3201\/eid0805.010284","article-title":"Evaluation in nonhuman primates of vaccines against Ebola virus","volume":"8","author":"Geisbert","year":"2002","journal-title":"Emerg. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5886","DOI":"10.1038\/s41598-017-06179-y","article-title":"High. dose sertraline monotherapy fails to protect rhesus macaques from lethal challenge with Ebola virus Makona","volume":"7","author":"Honko","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_20","first-page":"547","article-title":"Assessment and Optimization of the GeneXpert Diagnostic Platform for Detection of Ebola Virus RNA in Seminal Fluid","volume":"215","author":"Pettitt","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"s281","DOI":"10.1093\/infdis\/jiw267","article-title":"Pathogenicity Comparison Between the Kikwit and Makona Ebola Virus Variants in Rhesus Macaques","volume":"214","author":"Wong","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.3201\/eid2110.150259","article-title":"Delayed Disease Progression in Cynomolgus Macaques Infected with Ebola Virus Makona Strain","volume":"21","author":"Marzi","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Warren, T., Zumbrun, E., Weidner, J.M., Gomba, L., Rossi, F., Bannister, R., Tarrant, J., Reed, M., Lee, E., and Raymond, J.L. (2020). Characterization of Ebola Virus Disease (EVD) in Rhesus Monkeys for Development of EVD Therapeutics. Viruses, 12.","DOI":"10.3390\/v12010092"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/7\/753\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:51:06Z","timestamp":1760176266000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/7\/753"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,14]]},"references-count":23,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["v12070753"],"URL":"https:\/\/doi.org\/10.3390\/v12070753","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,14]]}}}