{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T12:21:01Z","timestamp":1784809261812,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012290","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T00:00:00Z","timestamp":1719187200000}}],"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T00:00:00Z","timestamp":1718064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100030643","name":"University of Kentucky Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100030643","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP23fk0108624"],"award-info":[{"award-number":["JP23fk0108624"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Ta\u00ef Forest virus (TAFV) is a negative-sense RNA virus in the <jats:italic>Filoviridae<\/jats:italic> family. TAFV has caused only a single human infection, but several disease outbreaks in chimpanzees have been linked to this virus. Limited research has been done on this human-pathogenic virus. We sought to establish an animal model to assess TAFV disease progression and pathogenicity at our facility. We had access to two different viral stock preparations from different institutions, both originating from the single human case. Type I interferon receptor knockout mice were inoculated with TAFV stock 1 or stock 2 by the intraperitoneal route. Inoculation resulted in 100% survival with no disease regardless of viral stock preparation or infectious dose. Next, cynomolgus macaques were inoculated with TAFV stock 1 or stock 2. Inoculation with TAFV stock 1 resulted in 100% survival and robust TAFV glycoprotein-specific IgG responses including neutralizing antibodies. In contrast, macaques infected with TAFV stock 2 developed disease and were euthanized 8\u201311 days after infection exhibiting viremia, thrombocytopenia, and increased inflammatory mediators identified by transcriptional analysis. Histopathologic analysis of tissue samples collected at necropsy confirmed classic filovirus disease in numerous organs. Genomic differences in both stock preparations were mapped to several viral genes which may have contributed to disease severity. Taken together, we demonstrate that infection with the two TAFV stocks resulted in no disease in mice and opposing disease phenotypes in cynomolgus macaques, highlighting the impact of viral stock propagation on pathogenicity in animal models.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012290","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T18:29:44Z","timestamp":1718130584000},"page":"e1012290","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pathogenic differences of cynomolgus macaques after Ta\u00ef Forest virus infection depend on the viral stock propagation"],"prefix":"10.1371","volume":"20","author":[{"given":"Paige","family":"Fletcher","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad S.","family":"Clancy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle L.","family":"O\u2019Donnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna M.","family":"Doratt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine C.","family":"Malherbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph F.","family":"Rhoderick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friederike","family":"Feldmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick W.","family":"Hanley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayato","family":"Takada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilhem","family":"Messaoudi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0186-9587","authenticated-orcid":true,"given":"Andrea","family":"Marzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,6,11]]},"reference":[{"key":"ppat.1012290.ref001","first-page":"232","article-title":"Ebola Virus (Filoviridae).","author":"A Marzi","journal-title":"Encyclopedia of Virology2021"},{"key":"ppat.1012290.ref002","doi-asserted-by":"crossref","first-page":"S48","DOI":"10.1086\/514285","article-title":"Human Infection Due to Ebola Virus, Subtype Co\u02c6te d\u2019Ivoire: Clinical and Biologic Presentation","volume":"179","author":"P Formenty","year":"1999","journal-title":"The Journal of Infectious Diseases"},{"issue":"4","key":"ppat.1012290.ref003","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1093\/femsre\/fuw010","article-title":"Neglected filoviruses.","volume":"40","author":"R Burk","year":"2016","journal-title":"FEMS Microbiol Rev"},{"key":"ppat.1012290.ref004","doi-asserted-by":"crossref","first-page":"S120","DOI":"10.1086\/514296","article-title":"Ebola Virus Outbreak among Wild Chimpanzees Living in a Rain Forest of Cote d\u2019Ivoire","volume":"179","author":"P Formenty","year":"1999","journal-title":"The Journal of Infectious Diseases"},{"issue":"1","key":"ppat.1012290.ref005","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":"G Wong","year":"2018","journal-title":"Zool Res"},{"issue":"14","key":"ppat.1012290.ref006","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":"TW Geisbert","year":"2009","journal-title":"J Virol"},{"issue":"2","key":"ppat.1012290.ref007","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":"JM Brannan","year":"2015","journal-title":"J Infect Dis"},{"issue":"2","key":"ppat.1012290.ref008","doi-asserted-by":"crossref","first-page":"2239950","DOI":"10.1080\/22221751.2023.2239950","article-title":"Single-dose VSV-based vaccine protects cynomolgus macaques from disease after Tai Forest virus infection","volume":"12","author":"P Fletcher","year":"2023","journal-title":"Emerg Microbes Infect"},{"issue":"10","key":"ppat.1012290.ref009","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1093\/cid\/ciw601","article-title":"Resurgence of Ebola Virus Disease in Guinea Linked to a Survivor With Virus Persistence in Seminal Fluid for More Than 500 Days","volume":"63","author":"B Diallo","year":"2016","journal-title":"Clin Infect Dis"},{"issue":"1","key":"ppat.1012290.ref010","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ajpath.2021.09.009","article-title":"Expanded Histopathology and Tropism of Ebola Virus in the Rhesus Macaque Model: Potential for Sexual Transmission, Altered Adrenomedullary Hormone Production, and Early Viral Replication in Liver","volume":"192","author":"DX Liu","year":"2022","journal-title":"Am J Pathol"},{"issue":"Supplement_7","key":"ppat.1012290.ref011","doi-asserted-by":"crossref","first-page":"S554","DOI":"10.1093\/infdis\/jiad118","article-title":"Establishing a Mouse Model for Sexual Transmission and Male Reproductive Tract Persistence of Ebola Virus","volume":"228","author":"CS Clancy","year":"2023","journal-title":"J Infect Dis"},{"issue":"36","key":"ppat.1012290.ref012","doi-asserted-by":"crossref","first-page":"33099","DOI":"10.1074\/jbc.M203775200","article-title":"Phosphorylation of VP30 impairs ebola virus transcription","volume":"277","author":"J Modrof","year":"2002","journal-title":"J Biol Chem"},{"issue":"11","key":"ppat.1012290.ref013","article-title":"The Roles of Ebola Virus Soluble Glycoprotein in Replication, Pathogenesis, and Countermeasure Development.","volume":"11","author":"W Zhu","year":"2019","journal-title":"Viruses"},{"issue":"3","key":"ppat.1012290.ref014","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":"VA Volchkova","year":"2011","journal-title":"J Infect Dis"},{"key":"ppat.1012290.ref015","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1099\/0022-1317-82-6-1365","article-title":"The role of type I interferon response in the resistance of mice to filovirus infection","volume":"82","author":"M. Bray","year":"2001","journal-title":"Journal of General Virology"},{"key":"ppat.1012290.ref016","doi-asserted-by":"crossref","DOI":"10.3390\/v11110987","article-title":"Generation and Characterization of a Mouse-Adapted Makona Variant of Ebola Virus.","volume":"11","author":"M Chan","year":"2019","journal-title":"Viruses"},{"key":"ppat.1012290.ref017","article-title":"Pathogenicity of Lloviu and Bombali viruses in IFNAR-\/- mice","author":"P Fletcher","year":"2023","journal-title":"J Infect Dis"},{"issue":"21","key":"ppat.1012290.ref018","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.126070","article-title":"Comparative pathogenesis of Ebola virus and Reston virus infection in humanized mice.","volume":"4","author":"B Escudero-Perez","year":"2019","journal-title":"JCI Insight."},{"issue":"2","key":"ppat.1012290.ref019","doi-asserted-by":"crossref","DOI":"10.3390\/microorganisms9020213","article-title":"Tai Forest Virus Does Not Cause Lethal Disease in Ferrets.","volume":"9","author":"Z Schiffman","year":"2021","journal-title":"Microorganisms."},{"issue":"1","key":"ppat.1012290.ref020","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13059-016-1137-3","article-title":"Transcriptomic signatures differentiate survival from fatal outcomes in humans infected with Ebola virus","volume":"18","author":"X Liu","year":"2017","journal-title":"Genome Biol"},{"issue":"10","key":"ppat.1012290.ref021","doi-asserted-by":"crossref","DOI":"10.3390\/pathogens9100850","article-title":"Immunological Perspective for Ebola Virus Infection and Various Treatment Measures Taken to Fight the Disease.","volume":"9","author":"S Jain","year":"2020","journal-title":"Pathogens"},{"issue":"1","key":"ppat.1012290.ref022","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1080\/22221751.2021.1942229","article-title":"Distinct transcriptional responses to fatal Ebola virus infection in cynomolgus and rhesus macaques suggest species-specific immune responses","volume":"10","author":"AN Pinski","year":"2021","journal-title":"Emerg Microbes Infect"},{"issue":"1","key":"ppat.1012290.ref023","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1146\/annurev-virology-092818-015708","article-title":"Ebola Virus: Pathogenesis and Countermeasure Development.","volume":"6","author":"W Furuyama","year":"2019","journal-title":"Annu Rev Virol"},{"issue":"6","key":"ppat.1012290.ref024","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.chom.2017.10.011","article-title":"Multi-platform \u2019Omics Analysis of Human Ebola Virus Disease Pathogenesis","volume":"22","author":"AJ Eisfeld","year":"2017","journal-title":"Cell Host Microbe"},{"issue":"4","key":"ppat.1012290.ref025","doi-asserted-by":"crossref","first-page":"e0151721","DOI":"10.1128\/mBio.01517-21","article-title":"Bundibugyo ebolavirus Survival Is Associated with Early Activation of Adaptive Immunity and Reduced Myeloid-Derived Suppressor Cell Signaling","volume":"12","author":"C Woolsey","year":"2021","journal-title":"mBio"},{"key":"ppat.1012290.ref026","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1186\/s12879-015-1169-4","article-title":"Ebola virus disease complicated with viral interstitial pneumonia: a case report.","volume":"15","author":"N Petrosillo","year":"2015","journal-title":"BMC Infect Dis"},{"key":"ppat.1012290.ref027","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/S0140-6736(95)90925-7","article-title":"Isolation and partial characterisation of a new strain of Ebola virus","volume":"345","author":"B Le Guenno","year":"1995","journal-title":"The Lancet"},{"issue":"8","key":"ppat.1012290.ref028","doi-asserted-by":"crossref","first-page":"e1002847","DOI":"10.1371\/journal.ppat.1002847","article-title":"The Ebola virus glycoprotein contributes to but is not sufficient for virulence in vivo","volume":"8","author":"A Groseth","year":"2012","journal-title":"PLoS Pathog"},{"issue":"5","key":"ppat.1012290.ref029","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.4269\/ajtmh.18-0937","article-title":"Gamma Irradiation as an Effective Method for Inactivation of Emerging Viral Pathogens","volume":"100","author":"F Feldmann","year":"2019","journal-title":"Am J Trop Med Hyg"},{"issue":"11","key":"ppat.1012290.ref030","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1128\/CVI.00170-10","article-title":"Enzyme-linked immunosorbent assay for detection of filovirus species-specific antibodies","volume":"17","author":"E Nakayama","year":"2010","journal-title":"Clin Vaccine Immunol"},{"issue":"3","key":"ppat.1012290.ref031","doi-asserted-by":"crossref","first-page":"e171","DOI":"10.1016\/S2666-5247(23)00001-0","article-title":"Species-specific immunogenicity and protective efficacy of a vesicular stomatitis virus-based Sudan virus vaccine: a challenge study in macaques","volume":"4","author":"A Marzi","year":"2023","journal-title":"Lancet Microbe"},{"issue":"11","key":"ppat.1012290.ref032","doi-asserted-by":"crossref","first-page":"5205","DOI":"10.1128\/JVI.75.11.5205-5214.2001","article-title":"Ebola virus VP40-induced particle formation and association with the lipid bilayer","volume":"75","author":"LD Jasenosky","year":"2001","journal-title":"J Virol"},{"issue":"10","key":"ppat.1012290.ref033","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":"A Marzi","year":"2015","journal-title":"Emerg Infect Dis"},{"key":"ppat.1012290.ref034","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1186\/1471-2105-7-191","article-title":"STEM: a tool for the analysis of short time series gene expression data","volume":"7","author":"J Ernst","year":"2006","journal-title":"BMC Bioinformatics"},{"issue":"1","key":"ppat.1012290.ref035","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"MD Robinson","year":"2010","journal-title":"Bioinformatics"},{"issue":"18","key":"ppat.1012290.ref036","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1093\/bioinformatics\/btu333","article-title":"Next maSigPro: updating maSigPro bioconductor package for RNA-seq time series","volume":"30","author":"MJ Nueda","year":"2014","journal-title":"Bioinformatics"},{"issue":"1","key":"ppat.1012290.ref037","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets.","volume":"10","author":"Y Zhou","year":"2019","journal-title":"Nat Commun"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1012290","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T00:00:00Z","timestamp":1719187200000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012290","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T19:41:12Z","timestamp":1719258072000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012290"}},"subtitle":[],"editor":[{"given":"Alexander","family":"Bukreyev","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,6,11]]},"references-count":37,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1012290","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1012290","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,11]]}}}