{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T08:26:15Z","timestamp":1789806375696,"version":"4.0.1"},"reference-count":55,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2015,12,19]],"date-time":"2015-12-19T00:00:00Z","timestamp":1450483200000},"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>Recent experimentation with the variants of the Ebola virus that differ in the glycoprotein\u2019s 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 na\u00efve and vaccinated cynomolgus macaques with either a 7U or 8U variant of the Ebola virus, Kikwit isolate. In na\u00efve 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.<\/jats:p>","DOI":"10.3390\/v7122969","type":"journal-article","created":{"date-parts":[[2015,12,21]],"date-time":"2015-12-21T10:43:59Z","timestamp":1450694639000},"page":"6739-6754","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Ebola Virus Infections in Nonhuman Primates Are Temporally Influenced by Glycoprotein Poly-U Editing Site Populations in the Exposure Material"],"prefix":"10.3390","volume":"7","author":[{"given":"John","family":"Trefry","sequence":"first","affiliation":[{"name":"Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3789-7400","authenticated-orcid":false,"given":"Steven","family":"Kern","sequence":"additional","affiliation":[{"name":"Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Bearss","sequence":"additional","affiliation":[{"name":"Pathology Division, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Jefferson","sequence":"additional","affiliation":[{"name":"Pathology Division, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Chance","sequence":"additional","affiliation":[{"name":"Pathology Division, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery","family":"Kugelman","sequence":"additional","affiliation":[{"name":"Molecular and Translational Sciences, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7751-4366","authenticated-orcid":false,"given":"Jason","family":"Ladner","sequence":"additional","affiliation":[{"name":"Molecular and Translational Sciences, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, 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Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1006\/viro.1995.0052","article-title":"GP mRNA of Ebola virus is edited by the Ebola virus polymerase and by T7 and vaccinia virus polymerases","volume":"214","author":"Volchkov","year":"1995","journal-title":"Virology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1006\/viro.1998.9143","article-title":"Release of viral glycoproteins during Ebola virus infection","volume":"245","author":"Volchkov","year":"1998","journal-title":"Virology"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Mohan, G.S., Li, W., Ye, L., Compans, R.W., and Yang, C. (2012). Antigenic subversion: A novel mechanism of host immune evasion by Ebola virus. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1003065"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kugelman, J.R., Lee, M.S., Rossi, C.A., McCarthy, S.E., Radoshitzky, S.R., Dye, J.M., Hensley, L.E., Honko, A., Kuhn, J.H., and Jahrling, P.B. (2012). Ebola virus genome plasticity as a marker of its passaging history: A comparison of in vitro passaging to non-human primate infection. PLoS One, 7.","DOI":"10.1371\/journal.pone.0050316"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1006\/viro.2000.0572","article-title":"Molecular characterization of guinea pig-adapted variants of Ebola virus","volume":"277","author":"Volchkov","year":"2000","journal-title":"Virology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S295","DOI":"10.1093\/infdis\/jiv216","article-title":"Genetic changes at the glycoprotein editing site associated with serial passage of Sudan virus","volume":"212","author":"Alfson","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_8","unstructured":"World Health Organization Ebola Situation Report\u201422 April 2015. Available online: http:\/\/apps.who.int\/ebola\/current-situation\/ebola-situation-report-22-april-2015-0."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nature13746","article-title":"Medical research: Ebola therapy protects severely ill monkeys","volume":"514","author":"Geisbert","year":"2014","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1093\/cid\/civ334","article-title":"The use of TKM-100802 and convalescent plasma in 2 patients with Ebola virus disease in the United States","volume":"61","author":"Kraft","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/nature14442","article-title":"Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates","volume":"521","author":"Thi","year":"2015","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Agnandji, S.T., Huttner, A., Zinser, M.E., Njuguna, P., Dahlke, C., Fernandes, J.F., Yerly, S., Dayer, J.A., Kraehling, V., and Kasonta, R. (2015). Phase 1 trials of rVSV Ebola vaccine in Africa and Europe\u2014Preliminary report. N. Engl. J. Med.","DOI":"10.1056\/NEJMoa1502924"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/nature14428","article-title":"Single-dose attenuated Vesiculovax vaccines protect primates against Ebola Makona virus","volume":"520","author":"Mire","year":"2015","journal-title":"Nature"},{"key":"ref_14","unstructured":"Regules, J.A., Beigel, J.H., Paolino, K.M., Voell, J., Castellano, A.R., Mu\u00f1oz, P., Moon, J.E., Ruck, R.C., Bennett, J.W., and Twomey, P.S. (2015). A recombinant vesicular stomatitis virus Ebola vaccine\u2014Preliminary report. N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1001\/jama.2015.1995","article-title":"Emergency postexposure vaccination with vesicular stomatitis virus-vectored Ebola vaccine after needlestick","volume":"313","author":"Lai","year":"2015","journal-title":"JAMA"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Warren, T.K., Whitehouse, C.A., Wells, J., Welch, L., Heald, A.E., Charleston, J.S., Sazani, P., Reid, S.P., Iversen, P.L., and Bavari, S. (2015). A single phosphorodiamidate morpholino oligomer targeting VP24 protects rhesus monkeys against lethal Ebola virus infection. MBio.","DOI":"10.1128\/mBio.02344-14"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1093\/infdis\/jiu511","article-title":"Safety and immunogenicity of DNA vaccines encoding Ebolavirus and Marburgvirus wild-type glycoproteins in a phase I clinical trial","volume":"211","author":"Sarwar","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1038\/nm.3702","article-title":"Chimpanzee adenovirus vaccine generates acute and durable protective immunity against Ebola virus challenge","volume":"20","author":"Stanley","year":"2014","journal-title":"Nat. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mire, C.E., Geisbert, J.B., Agans, K.N., Satterfield, B.A., Versteeg, K.M., Fritz, E.A., Feldmann, H., Hensley, L.E., and Geisbert, T.W. (2014). Durability of a vesicular stomatitis virus-based Marburg virus vaccine in nonhuman primates. PLoS One, 9.","DOI":"10.1371\/journal.pone.0094355"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/nature13027","article-title":"Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430","volume":"508","author":"Warren","year":"2014","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nature13777","article-title":"Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp","volume":"514","author":"Qiu","year":"2014","journal-title":"Nature"},{"key":"ref_22","unstructured":"Rampling, T., Ewer, K., Bowyer, G., Wright, D., Imoukhuede, E.B., Payne, R., Hartnell, F., Gibani, M., Bliss, C., and Minhinnick, A. (2015). A monovalent chimpanzee adenovirus Ebola vaccine\u2014Preliminary report. N. Engl. J. Med."},{"key":"ref_23","unstructured":"Food and Drug Administration (2014). Guidance for Industry Product Development Under the Animal Rule, Available online: http:\/\/www.fda.gov\/downloads\/drugs\/guidancecomplianceregulatoryinformation\/guidances\/ucm399217.pdf."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.coviro.2013.01.001","article-title":"Animal models for highly pathogenic emerging viruses","volume":"3","author":"Safronetz","year":"2013","journal-title":"Curr. Opin. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5034","DOI":"10.1073\/pnas.1200409109","article-title":"Postexposure antibody prophylaxis protects nonhuman primates from filovirus disease","volume":"109","author":"Dye","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Feldmann, H., Jones, S.M., Daddario-DiCaprio, K.M., Geisbert, J.B., Stroher, U., Grolla, A., Bray, M., Fritz, E.A., Fernando, L., and Feldmann, F. (2007). Effective post-exposure treatment of Ebola infection. PLoS Pathog., 3.","DOI":"10.1371\/journal.ppat.0030002"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1016\/S0140-6736(03)15012-X","article-title":"Treatment of Ebola virus infection with a recombinant inhibitor of factor VIIa\/tissue factor: A study in rhesus monkeys","volume":"362","author":"Geisbert","year":"2003","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1016\/S0140-6736(10)60357-1","article-title":"Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: A proof-of-concept study","volume":"375","author":"Geisbert","year":"2010","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S390","DOI":"10.1086\/520598","article-title":"Recombinant human activated protein C for the postexposure treatment of Ebola hemorrhagic fever","volume":"196","author":"Hensley","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Marzi, A., Yoshida, R., Miyamoto, H., Ishijima, M., Suzuki, Y., Higuchi, M., Matsuyama, Y., Igarashi, M., Nakayama, E., and Kuroda, M. (2012). Protective efficacy of neutralizing monoclonal antibodies in a nonhuman primate model of Ebola hemorrhagic fever. PLoS One, 7.","DOI":"10.1371\/journal.pone.0036192"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1128\/CVI.00467-09","article-title":"Protection of nonhuman primates against two species of Ebola virus infection with a single complex adenovirus vector","volume":"17","author":"Pratt","year":"2010","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1093\/infdis\/jis921","article-title":"Interferon-beta therapy prolongs survival in rhesus macaque models of Ebola and Marburg hemorrhagic fever","volume":"208","author":"Smith","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/nm.2202","article-title":"Advanced antisense therapies for postexposure protection against lethal filovirus infections","volume":"16","author":"Warren","year":"2010","journal-title":"Nat. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6894","DOI":"10.1016\/j.vaccine.2008.09.082","article-title":"Vesicular stomatitis virus-based vaccines protect nonhuman primates against aerosol challenge with Ebola and Marburg viruses","volume":"26","author":"Geisbert","year":"2008","journal-title":"Vaccine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7296","DOI":"10.1128\/JVI.00561-09","article-title":"Single-injection vaccine protects nonhuman primates against infection with Marburg virus and three species of Ebola virus","volume":"83","author":"Geisbert","year":"2009","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/nm1258","article-title":"Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses","volume":"11","author":"Jones","year":"2005","journal-title":"Nat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/nature01876","article-title":"Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates","volume":"424","author":"Sullivan","year":"2003","journal-title":"Nature"},{"key":"ref_38","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_39","doi-asserted-by":"crossref","first-page":"3511","DOI":"10.3390\/v4123511","article-title":"Standardization of the filovirus plaque assay for use in preclinical studies","volume":"4","author":"Shurtleff","year":"2012","journal-title":"Viruses"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6773","DOI":"10.1128\/JVI.00649-15","article-title":"Particle-to-PFU ratio of Ebola virus influences disease course and survival in cynomolgus macaques","volume":"89","author":"Alfson","year":"2015","journal-title":"J. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4666","DOI":"10.3390\/v6114666","article-title":"Euthanasia assessment in Ebola virus infected nonhuman primates","volume":"6","author":"Warren","year":"2014","journal-title":"Viruses"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1517\/17460441.2011.554815","article-title":"Nonhuman primates as models for the discovery and development of Ebola virus therapeutics","volume":"6","author":"Shurtleff","year":"2011","journal-title":"Expert. Opin. Drug Discov."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Cooper, B.S., Boni, M.F., Pan-Ngum, W., Day, N.P., Horby, P.W., Olliaro, P., Lang, T., White, N.J., White, L.J., and Whitehead, J. (2015). Evaluating clinical trial designs for investigational treatments of Ebola virus disease. PLoS Med., 12.","DOI":"10.1371\/journal.pmed.1001815"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.tim.2014.12.005","article-title":"A race for an Ebola vaccine: Promises and obstacles","volume":"23","author":"Cooper","year":"2015","journal-title":"Trends Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"S941","DOI":"10.1093\/infdis\/jir321","article-title":"Genomic RNA editing and its impact on Ebola virus adaptation during serial passages in cell culture and infection of guinea pigs","volume":"204","author":"Volchkova","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1126\/science.1057269","article-title":"Recovery of infectious Ebola virus from complementary DNA: RNA editing of the GP gene and viral cytotoxicity","volume":"291","author":"Volchkov","year":"2001","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.antiviral.2012.01.011","article-title":"The role of antigen-presenting cells in filoviral hemorrhagic fever: Gaps in current knowledge","volume":"93","author":"Martinez","year":"2012","journal-title":"Antiviral Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1016\/j.biocel.2005.02.018","article-title":"Ebola virus: The role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever","volume":"37","author":"Bray","year":"2005","journal-title":"Int. J. Biochem. Cell. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Escudero-Perez, B., Volchkova, V.A., Dolnik, O., Lawrence, P., and Volchkov, V.E. (2014). Shed GP of Ebola virus triggers immune activation and increased vascular permeability. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004509"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Rubins, K.H., Hensley, L.E., Wahl-Jensen, V., Daddario DiCaprio, K.M., Young, H.A., Reed, D.S., Jahrling, P.B., Brown, P.O., Relman, D.A., and Geisbert, T.W. (2007). The temporal program of peripheral blood gene expression in the response of nonhuman primates to Ebola hemorrhagic fever. Genome Biol., 8.","DOI":"10.1186\/gb-2007-8-8-r174"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Volchkova, V.A., Dolnik, O., Martinez, M.J., Reynard, O., and Volchkov, V.E. (2015). RNA editing of the GP gene of Ebola virus is an important pathogenicity factor. J. Infect. Dis.","DOI":"10.1093\/infdis\/jiv309"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1242\/dmm.000471","article-title":"Disease modeling for Ebola and Marburg viruses","volume":"2","author":"Bente","year":"2009","journal-title":"Dis. Model Mech."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/path.4456","article-title":"Tissue and cellular tropism, pathology and pathogenesis of Ebola and Marburg viruses","volume":"235","author":"Martines","year":"2015","journal-title":"J. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Hoenen, T., Marzi, A., Scott, D.P., Feldmann, F., Callison, J., Safronetz, D., Ebihara, H., and Feldmann, H. (2015). Soluble glycoprotein is not required for Ebola virus virulence in Guinea pigs. J. Infect. Dis.","DOI":"10.1093\/infdis\/jiv111"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Tsuda, Y., Hoenen, T., Banadyga, L., Weisend, C., Ricklefs, S.M., Porcella, S.F., and Ebihara, H. (2015). An improved reverse genetics system to overcome cell-type-dependent Ebola virus genome plasticity. J. Infect. Dis.","DOI":"10.1093\/infdis\/jiu681"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/7\/12\/2969\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:54:24Z","timestamp":1760216064000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/7\/12\/2969"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,19]]},"references-count":55,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2015,12]]}},"alternative-id":["v7122969"],"URL":"https:\/\/doi.org\/10.3390\/v7122969","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,19]]}}}