{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T09:28:38Z","timestamp":1780824518863,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013916","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000}}],"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100011094","name":"Public Health Agency of Canada","doi-asserted-by":"crossref","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100011094","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19 AI142790-03"],"award-info":[{"award-number":["U19 AI142790-03"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","award":["CB11408"],"award-info":[{"award-number":["CB11408"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Ebola virus (EBOV) infection typically results in severe\u2014and often lethal\u2014acute disease. However, increasing evidence suggests that EBOV can persist in certain immune-privileged tissues, which may then serve as reservoirs for the later reemergence of EBOV and disease recrudescence. Here, we report atypical EVD recrudescence in a ferret model inoculated with an otherwise lethal dose of EBOV and treated with low doses of a highly potent monoclonal antibody cocktail. Among 32 antibody-treated ferrets, 14 animals survived, while 8 succumbed to acute EVD within about 5\u20138 days. The remaining 10 animals succumbed to atypical EVD between 12 and 18 days post-infection (DPI) despite having shown no, or very minor, signs of illness during the acute phase of disease. While viremia disappeared by 14 DPI in most animals that succumbed to atypical EVD, it rebounded modestly just prior to death. Unlike animals that died of acute EVD, those that died of atypical EVD showed only a moderate systemic inflammatory response and few signs of organ dysfunction, in line with low levels of virus in the liver and spleen. Interestingly, however, ferrets that died of atypical EVD showed high levels of virus in the brain, consistent with increased markers of inflammation in the central nervous system and significant pathological changes, including a breakdown in the blood-brain barrier and severe meningoencephalitis. Not only does this study shed important light on the atypical and underappreciated manifestations of EVD, but it also establishes the ferret as a valuable model of EBOV recrudescence.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013916","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T17:49:11Z","timestamp":1777916951000},"page":"e1013916","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of atypical Ebola virus disease in ferrets"],"prefix":"10.1371","volume":"22","author":[{"given":"Wenguang","family":"Cao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihua","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Schulz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Wight","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla","family":"Emeterio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guodong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Audet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Tierney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Azaransky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Frost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilianne","family":"Gee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"McQueen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Chong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah B.","family":"Sulkosky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Booth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garrett","family":"Westmacott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica Ollmann","family":"Saphire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiankun","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8390-2648","authenticated-orcid":true,"given":"Logan","family":"Banadyga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"ppat.1013916.ref001","article-title":"Filoviridae.","volume-title":"Fields virology","author":"JH Kuhn","year":"2021"},{"issue":"1721","key":"ppat.1013916.ref002","doi-asserted-by":"crossref","DOI":"10.1098\/rstb.2016.0297","article-title":"The Ebola outbreak, 2013-2016: old lessons for new epidemics","volume":"372","author":"CE Coltart","year":"2017","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"ppat.1013916.ref003","unstructured":"Organization WH. 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Integrated review: BLA-761169 Inmazeb (Atoltivimab, Maftivimab, and odesivimab-ebgn). 2020."},{"issue":"8","key":"ppat.1013916.ref040","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/S1473-3099(18)30397-9","article-title":"Safety, pharmacokinetics, and immunogenicity of a co-formulated cocktail of three human monoclonal antibodies targeting Ebola virus glycoprotein in healthy adults: a randomised, first-in-human phase 1 study","volume":"18","author":"S Sivapalasingam","year":"2018","journal-title":"Lancet Infect Dis"},{"issue":"10174","key":"ppat.1013916.ref041","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0140-6736(19)30036-4","article-title":"Safety, tolerability, pharmacokinetics, and immunogenicity of the therapeutic monoclonal antibody mAb114 targeting Ebola virus glycoprotein (VRC 608): an open-label phase 1 study","volume":"393","author":"MR Gaudinski","year":"2019","journal-title":"Lancet"},{"issue":"2","key":"ppat.1013916.ref042","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3201\/eid3102.240983","article-title":"Sudan virus persistence in immune-privileged organs of nonhuman primate survivors","volume":"31","author":"BB Beavis","year":"2025","journal-title":"Emerg Infect Dis"},{"issue":"1","key":"ppat.1013916.ref043","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1038\/s41467-021-22132-0","article-title":"Combination therapy protects macaques against advanced Marburg virus disease","volume":"12","author":"RW Cross","year":"2021","journal-title":"Nat Commun"},{"issue":"10","key":"ppat.1013916.ref044","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.159090","article-title":"Combination therapy with remdesivir and monoclonal antibodies protects nonhuman primates against advanced Sudan virus disease","volume":"7","author":"RW Cross","year":"2022","journal-title":"JCI Insight"},{"issue":"7877","key":"ppat.1013916.ref045","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/s41586-021-03901-9","article-title":"Resurgence of Ebola virus in 2021 in Guinea suggests a new paradigm for outbreaks","volume":"597","author":"AK Keita","year":"2021","journal-title":"Nature"},{"issue":"12","key":"ppat.1013916.ref046","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.3201\/eid2212.160847","article-title":"Unusual Ebola virus chain of transmission, Conakry, Guinea, 2014-2015","volume":"22","author":"M Keita","year":"2016","journal-title":"Emerg Infect Dis"},{"issue":"3","key":"ppat.1013916.ref047","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","article-title":"A simple method of estimating fifty per cent endpoints","volume":"27","author":"LJ Reed","year":"1938","journal-title":"Am J Epidemiol"},{"key":"ppat.1013916.ref048","doi-asserted-by":"crossref","first-page":"114348","DOI":"10.1016\/j.jviromet.2021.114348","article-title":"Optimisation of methodology for whole genome sequencing of Measles Virus directly from patient specimens","volume":"299","author":"H Schulz","year":"2022","journal-title":"J Virol Methods"},{"key":"ppat.1013916.ref049","volume-title":"R: a language and environment for statistical computing","author":"R Core Team","year":"2024"},{"issue":"43","key":"ppat.1013916.ref050","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.21105\/joss.01686","article-title":"Welcome to the tidyverse","volume":"4","author":"H Wickham","year":"2019","journal-title":"JOSS"},{"key":"ppat.1013916.ref051","author":"M DeBerardine","year":"2023","journal-title":"BRGenomics: tools for the efficient analysis of high-resolution genomics data"},{"issue":"12","key":"ppat.1013916.ref052","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"key":"ppat.1013916.ref053","author":"R Kolde","year":"2019","journal-title":"pheatmap: Pretty heatmaps"},{"key":"ppat.1013916.ref054","author":"H Wickham","year":"2023","journal-title":"dplyr: A grammar of data manipulation"},{"issue":"14","key":"ppat.1013916.ref055","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1093\/bioinformatics\/btp328","article-title":"rtracklayer: an R package for interfacing with genome browsers","volume":"25","author":"M Lawrence","year":"2009","journal-title":"Bioinformatics"},{"issue":"1","key":"ppat.1013916.ref056","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1074\/mcp.TIR119.001616","article-title":"Sample preparation by easy extraction and digestion (SPEED) - 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