{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:19:29Z","timestamp":1790965169602,"version":"4.1.0"},"reference-count":63,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,2,3]],"date-time":"2019-02-03T00:00:00Z","timestamp":1549152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HHSN272201000040I\/HHSN27200008"],"award-info":[{"award-number":["HHSN272201000040I\/HHSN27200008"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The 2014 Ebolavirus outbreak in West Africa highlighted the need for vaccines and therapeutics to prevent and treat filovirus infections. A well-characterized small animal model that is susceptible to wild-type filoviruses would facilitate the screening of anti-filovirus agents. To that end, we characterized knockout mice lacking \u03b1\/\u03b2 and \u03b3 interferon receptors (IFNAGR KO) as a model for wild-type filovirus infection. Intraperitoneal challenge of IFNAGR KO mice with several known human pathogenic species from the genus Ebolavirus and Marburgvirus, except Bundibugyo ebolavirus and Ta\u00ef Forest ebolavirus, caused variable mortality rate. Further characterization of the prototype Ebola virus Kikwit isolate infection in this KO mouse model showed 100% lethality down to a dilution equivalent to 1.0 \u00d7 10\u22121 pfu with all deaths occurring between 7 and 9 days post-challenge. Viral RNA was detectable in serum after challenge with 1.0 \u00d7 102 pfu as early as one day after infection. Changes in hematology and serum chemistry became pronounced as the disease progressed and mirrored the histological changes in the spleen and liver that were also consistent with those described for patients with Ebola virus disease. In a proof-of-principle study, treatment of Ebola virus infected IFNAGR KO mice with favipiravir resulted in 83% protection. Taken together, the data suggest that IFNAGR KO mice may be a useful model for early screening of anti-filovirus medical countermeasures.<\/jats:p>","DOI":"10.3390\/v11020137","type":"journal-article","created":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T11:31:07Z","timestamp":1549366267000},"page":"137","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Filovirus Virulence in Interferon \u03b1\/\u03b2 and \u03b3 Double Knockout Mice, and Treatment with Favipiravir"],"prefix":"10.3390","volume":"11","author":[{"given":"Jason E.","family":"Comer","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"},{"name":"Office of Regulated Nonclinical Studies, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"},{"name":"Sealy Institute for Vaccine Science, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"},{"name":"The Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0402-9698","authenticated-orcid":false,"given":"Olivier","family":"Escaffre","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Neef","sequence":"additional","affiliation":[{"name":"Experimental Pathology Laboratories, Inc., Sterling, VA 20167, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor","family":"Brasel","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"},{"name":"Office of Regulated Nonclinical Studies, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"},{"name":"Sealy Institute for Vaccine Science, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry L.","family":"Juelich","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer K.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanon","family":"Smith","sequence":"additional","affiliation":[{"name":"Office of Regulated Nonclinical Studies, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birte","family":"Kalveram","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D.","family":"Perez","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane","family":"Massey","sequence":"additional","affiliation":[{"name":"Office of Regulated Nonclinical Studies, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander N.","family":"Freiberg","sequence":"additional","affiliation":[{"name":"Sealy Institute for Vaccine Science, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"},{"name":"The Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"},{"name":"Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"},{"name":"Institute for Human Infections and Immunity, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,3]]},"reference":[{"key":"ref_1","first-page":"1229","article-title":"Virus nomenclature below the species level: A standardized nomenclature for filovirus strains and variants rescued from cdna","volume":"159","author":"Kuhn","year":"2014","journal-title":"Arch. Virol."},{"key":"ref_2","unstructured":"CDC (2018, June 27). 2014 Ebola Outbreak in West Africa\u2014Case Counts, Available online: https:\/\/www.cdc.gov\/vhf\/ebola\/history\/2014-2016-outbreak\/case-counts.html."},{"key":"ref_3","first-page":"13","article-title":"Filoviruses. A compendium of 40 years of epidemiological, clinical, and laboratory studies","volume":"20","author":"Kuhn","year":"2008","journal-title":"Arch. Virol. Suppl."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6497","DOI":"10.1128\/JVI.00069-06","article-title":"Marburgvirus genomics and association with a large hemorrhagic fever outbreak in angola","volume":"80","author":"Towner","year":"2006","journal-title":"J. Virol."},{"key":"ref_5","unstructured":"Centers for Disease Control (CDC) (1990). Update: Filovirus infection in animal handlers. MMWR Morb. Mortal. Wkly. Rep., 39, 221."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/0140-6736(91)91199-5","article-title":"Seroepidemiological study of filovirus related to ebola in the philippines","volume":"337","author":"Miranda","year":"1991","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.coviro.2016.11.013","article-title":"Human transmission of ebola virus","volume":"22","author":"Lawrence","year":"2017","journal-title":"Curr. Opin. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1146\/annurev-pathol-052016-100506","article-title":"The pathogenesis of ebola virus disease","volume":"12","author":"Baseler","year":"2017","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Matassov, D., Mire, C.E., Latham, T., Geisbert, J.B., Xu, R., Ota-Setlik, A., Agans, K.N., Kobs, D.J., Wendling, M.Q.S., and Burnaugh, A. (2017). Single dose trivalent vesiculovax vaccine protects macaques from lethal ebolavirus and marburgvirus challenge. J. Virol.","DOI":"10.1128\/JVI.01190-17"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3389\/fmicb.2013.00267","article-title":"Animal models for ebola and marburg virus infections","volume":"4","author":"Nakayama","year":"2013","journal-title":"Front. Microbiol."},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"9209","DOI":"10.1128\/JVI.01033-16","article-title":"Ferrets infected with bundibugyo virus or ebola virus recapitulate important aspects of human filovirus disease","volume":"90","author":"Kozak","year":"2016","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"46262","DOI":"10.18632\/oncotarget.17694","article-title":"Characterization of sudan ebolavirus infection in ferrets","volume":"8","author":"Kroeker","year":"2017","journal-title":"Oncotarget"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1080\/17460441.2018.1527827","article-title":"Small animal models of filovirus disease: Recent advances and future directions","volume":"13","author":"Cross","year":"2018","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1093\/infdis\/jis626","article-title":"A syrian golden hamster model recapitulating ebola hemorrhagic fever","volume":"207","author":"Ebihara","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"39214","DOI":"10.1038\/srep39214","article-title":"A hamster model for marburg virus infection accurately recapitulates marburg hemorrhagic fever","volume":"6","author":"Marzi","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S968","DOI":"10.1093\/infdis\/jir330","article-title":"Assessment of rodents as animal models for reston ebolavirus","volume":"204","author":"Munster","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S1090","DOI":"10.1093\/infdis\/jir379","article-title":"Protective efficacy of a bivalent recombinant vesicular stomatitis virus vaccine in the syrian hamster model of lethal ebola virus infection","volume":"204","author":"Tsuda","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8059607","DOI":"10.1155\/2016\/8059607","article-title":"Adapted lethality: What we can learn from guinea pig-adapted ebola virus infection model","volume":"2016","author":"Cheresiz","year":"2016","journal-title":"Adv. Virol."},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"S305","DOI":"10.1093\/infdis\/jiv237","article-title":"Modeling the disease course of zaire ebolavirus infection in the outbred guinea pig","volume":"212","author":"Cross","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1186\/s13059-014-0540-x","article-title":"Elucidating variations in the nucleotide sequence of ebola virus associated with increasing pathogenicity","volume":"15","author":"Dowall","year":"2014","journal-title":"Genome Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S1011","DOI":"10.1093\/infdis\/jir338","article-title":"Vp24 is a molecular determinant of ebola virus virulence in guinea pigs","volume":"204","author":"Mateo","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S384","DOI":"10.1093\/infdis\/jiv126","article-title":"A single-vector, single-injection trivalent filovirus vaccine: Proof of concept study in outbred guinea pigs","volume":"212","author":"Mire","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_25","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_26","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_27","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1128\/JVI.02331-15","article-title":"Development and characterization of a guinea pig-adapted sudan virus","volume":"90","author":"Wong","year":"2016","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.3390\/v4091477","article-title":"Mouse models for filovirus infections","volume":"4","author":"Bradfute","year":"2012","journal-title":"Viruses"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1099\/0022-1317-82-6-1365","article-title":"The role of the type i interferon response in the resistance of mice to filovirus infection","volume":"82","author":"Bray","year":"2001","journal-title":"J. Gen. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S248","DOI":"10.1086\/514292","article-title":"A mouse model for evaluation of prophylaxis and therapy of ebola hemorrhagic fever","volume":"179","author":"Bray","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3449","DOI":"10.1016\/j.jmb.2016.05.008","article-title":"Rodent-adapted filoviruses and the molecular basis of pathogenesis","volume":"428","author":"Banadyga","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3468","DOI":"10.3390\/v4123468","article-title":"Development of a murine model for aerosolized ebolavirus infection using a panel of recombinant inbred mice","volume":"4","author":"Zumbrun","year":"2012","journal-title":"Viruses"},{"key":"ref_33","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_34","first-page":"253","article-title":"Animal models of ebolavirus infection","volume":"67","author":"Ragland","year":"2017","journal-title":"Comp. Med."},{"key":"ref_35","unstructured":"Groseth, A., Eickmann, M., Ebihara, H., Becker, S., and Hoenen, T. (2001). Filoviruses: Ebola, marburg and disease. Encyclopedia of Life Sciences, John Wiley & Sons, Ltd."},{"key":"ref_36","first-page":"3","article-title":"Type i interferon receptor knockout mice as models for infection of highly pathogenic viruses with outbreak potential","volume":"39","author":"Wong","year":"2018","journal-title":"Zool. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S986","DOI":"10.1093\/infdis\/jir335","article-title":"Filovirus infection of stat-1 knockout mice","volume":"204","author":"Raymond","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S282","DOI":"10.1093\/infdis\/jiv215","article-title":"Interferon alpha\/beta receptor-deficient mice as a model for ebola virus disease","volume":"212","author":"Brannan","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"S296","DOI":"10.1086\/520602","article-title":"Lymphocyte death in a mouse model of ebola virus infection","volume":"196","author":"Bradfute","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_40","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_41","doi-asserted-by":"crossref","first-page":"S404","DOI":"10.1093\/infdis\/jiv188","article-title":"Stat1-deficient mice are not an appropriate model for efficacy testing of recombinant vesicular stomatitis virus-based filovirus vaccines","volume":"212","author":"Marzi","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e01711-17","DOI":"10.1128\/AAC.01711-17","article-title":"Efficacy of tilorone dihydrochloride against ebola virus infection","volume":"62","author":"Ekins","year":"2018","journal-title":"Antimicrob Agents Chemother."},{"key":"ref_43","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_44","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_45","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.antiviral.2015.08.015","article-title":"Ebola virus dynamics in mice treated with favipiravir","volume":"123","author":"Madelain","year":"2015","journal-title":"Antivir. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.antiviral.2014.01.012","article-title":"Post-exposure efficacy of oral t-705 (favipiravir) against inhalational ebola virus infection in a mouse model","volume":"104","author":"Smither","year":"2014","journal-title":"Antivir. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.antiviral.2014.02.014","article-title":"Successful treatment of advanced ebola virus infection with t-705 (favipiravir) in a small animal model","volume":"105","author":"Oestereich","year":"2014","journal-title":"Antivir. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.antiviral.2017.12.020","article-title":"Intracellular conversion and in vivo dose response of favipiravir (t-705) in rodents infected with ebola virus","volume":"151","author":"Bixler","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.antiviral.2018.01.011","article-title":"Successful treatment of marburg virus with orally administrated t-705 (favipiravir) in a mouse model","volume":"151","author":"Zhu","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"S649","DOI":"10.1093\/infdis\/jiy303","article-title":"Postexposure protective efficacy of t-705 (favipiravir) against sudan virus infection in guinea pigs","volume":"218","author":"Rahim","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Guedj, J., Piorkowski, G., Jacquot, F., Madelain, V., Nguyen, T.H.T., Rodallec, A., Gunther, S., Carbonnelle, C., Mentre, F., and Raoul, H. (2018). Antiviral efficacy of favipiravir against ebola virus: A translational study in cynomolgus macaques. PLoS Med., 15.","DOI":"10.1371\/journal.pmed.1002535"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.antiviral.2017.12.021","article-title":"Efficacy of favipiravir (t-705) in nonhuman primates infected with ebola virus or marburg virus","volume":"151","author":"Bixler","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6404","DOI":"10.1128\/JVI.00126-09","article-title":"Development and characterization of a mouse model for marburg hemorrhagic fever","volume":"83","author":"Warfield","year":"2009","journal-title":"J. Virol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ebihara, H., Takada, A., Kobasa, D., Jones, S., Neumann, G., Theriault, S., Bray, M., Feldmann, H., and Kawaoka, Y. (2006). Molecular determinants of ebola virus virulence in mice. PLoS Pathog., 2.","DOI":"10.1371\/journal.ppat.0020073"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4309","DOI":"10.1128\/JVI.02575-10","article-title":"Marburg virus vp40 antagonizes interferon signaling in a species-specific manner","volume":"85","author":"Valmas","year":"2011","journal-title":"J. Virol."},{"key":"ref_56","first-page":"S438","article-title":"Natural history and pathogenesis of wild-type marburg virus infection in stat2 knockout hamsters","volume":"218","author":"Atkins","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1099\/jmm.0.036210-0","article-title":"Lethality and pathogenesis of airborne infection with filoviruses in a129 alpha\/beta -\/- interferon receptor-deficient mice","volume":"61","author":"Lever","year":"2012","journal-title":"J. Med. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Rhein, B.A., Powers, L.S., Rogers, K., Anantpadma, M., Singh, B.K., Sakurai, Y., Bair, T., Miller-Hunt, C., Sinn, P., and Davey, R.A. (2015). Interferon-gamma inhibits ebola virus infection. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005263"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Alfson, K.J., Avena, L.E., Beadles, M.W., Worwa, G., Amen, M., Patterson, J.L., Carrion, R., and Griffiths, A. (2018). Intramuscular exposure of macaca fascicularis to low doses of low passage- or cell culture-adapted sudan virus or ebola virus. Viruses, 10.","DOI":"10.3390\/v10110642"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1093\/infdis\/152.5.887","article-title":"Pathophysiology of shock and hemorrhage in a fulminating viral infection (ebola)","volume":"152","author":"Platt","year":"1985","journal-title":"J. Infect. Dis."},{"key":"ref_61","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_62","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_63","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.antiviral.2013.09.015","article-title":"Favipiravir (t-705), a novel viral rna polymerase inhibitor","volume":"100","author":"Furuta","year":"2013","journal-title":"Antivir. Res."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/2\/137\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:30:55Z","timestamp":1760185855000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/2\/137"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,3]]},"references-count":63,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,2]]}},"alternative-id":["v11020137"],"URL":"https:\/\/doi.org\/10.3390\/v11020137","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,3]]}}}