{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:05:13Z","timestamp":1791666313843,"version":"4.3.4"},"reference-count":52,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"631","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2022,2,9]]},"abstract":"<jats:p>Effective therapeutics have been developed against acute Ebola virus disease (EVD) in both humans and experimentally infected nonhuman primates. However, the risk of viral persistence and associated disease recrudescence in survivors receiving these therapeutics remains unclear. In contrast to rhesus macaques that survived Ebola virus (EBOV) exposure in the absence of treatment, we discovered that EBOV, despite being cleared from all other organs, persisted in the brain ventricular system of rhesus macaque survivors that had received monoclonal antibody (mAb) treatment. In mAb-treated macaque survivors, EBOV persisted in macrophages infiltrating the brain ventricular system, including the choroid plexuses. This macrophage infiltration was accompanied by severe tissue damage, including ventriculitis, choroid plexitis, and meningoencephalitis. Specifically, choroid plexus endothelium-derived EBOV infection led to viral persistence in the macaque brain ventricular system. This resulted in apoptosis of ependymal cells, which constitute the blood\u2013cerebrospinal fluid barrier of the choroid plexuses. Fatal brain-confined recrudescence of EBOV infection manifested as severe inflammation, local pathology, and widespread infection of the ventricular system and adjacent neuropil in some of the mAb-treated macaque survivors. This study highlights organ-specific EBOV persistence and fatal recrudescent disease in rhesus macaque survivors after therapeutic treatment and has implications for the long-term follow-up of human survivors of EVD.<\/jats:p>","DOI":"10.1126\/scitranslmed.abi5229","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T18:55:26Z","timestamp":1644432926000},"source":"Crossref","is-referenced-by-count":54,"title":["Ebola virus persistence and disease recrudescence in the brains of antibody-treated nonhuman primate survivors"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5206-3028","authenticated-orcid":true,"given":"Jun","family":"Liu","sequence":"first","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Trefry","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4614-9559","authenticated-orcid":true,"given":"April M.","family":"Babka","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher W.","family":"Schellhase","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla M.","family":"Coffin","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice A.","family":"Williams","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2669-9062","authenticated-orcid":true,"given":"Jo Lynne W.","family":"Raymond","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2607-8431","authenticated-orcid":true,"given":"Paul R.","family":"Facemire","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor B.","family":"Chance","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4722-746X","authenticated-orcid":true,"given":"Neil M.","family":"Davis","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1733-7614","authenticated-orcid":true,"given":"Jennifer L.","family":"Scruggs","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco D.","family":"Rossi","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8957-2608","authenticated-orcid":true,"given":"Andrew D.","family":"Haddow","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine M.","family":"Zelko","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1960-1311","authenticated-orcid":true,"given":"Sandra L.","family":"Bixler","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2485-4011","authenticated-orcid":true,"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":"Patrick L.","family":"Iversen","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0080-3260","authenticated-orcid":true,"given":"Margaret L.","family":"Pitt","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7800-6045","authenticated-orcid":true,"given":"Jens H.","family":"Kuhn","sequence":"additional","affiliation":[{"name":"Integrated Research Facility at Fort Detrick (IRF-Frederick), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5062-1938","authenticated-orcid":true,"given":"Gustavo","family":"Palacios","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3526-8755","authenticated-orcid":true,"given":"Xiankun","family":"Zeng","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","unstructured":"J. H. Kuhn G. K. Amarasinghe D. L. Perry in Fields VIROLOGY P. M. Howley D. M. Knipe S. P. J. Whelan Eds. (Wolters Kluwer\/Lippincott Williams & Wilkins 2020) vol. 1 (Emerging Viruses) chap. 11 pp. 449\u2013503."},{"key":"e_1_3_3_3_2","unstructured":"World Health Organization Ebola situation report https:\/\/apps.who.int\/iris\/handle\/10665\/204714."},{"key":"e_1_3_3_4_2","unstructured":"World Health Organization Ebola in the Democratic Republic of the Congo. North Kivu Ituri 2018\u20132020; https:\/\/www.who.int\/emergencies\/situations\/Ebola-2019-drc-."},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/v10120683"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-0147-3"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/514291"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/514318"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1511410"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw202"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2015.20.48.30083"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw601"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1805435"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/ve\/vew016"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1600378"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2502.181011"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30417-1"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2017.09.013"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509773"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw078"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy280"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsbl.2015.1079"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30386-5"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1500306"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(79)92335-3"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02122443"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1910993"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2024670"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30313-5"},{"key":"e_1_3_3_30_2","unstructured":"World Health Organization Resurgence of Ebola in North Kivu in the Democratic Republic of the Congo (2021); www.afro.who.int\/news\/resurgence-ebola-north-kivu-democratic-republic-congo."},{"key":"e_1_3_3_31_2","unstructured":"World Health Organization Ebola \u2013 Guinea (2021); www.who.int\/emergencies\/disease-outbreak-news\/item\/2021-DON328."},{"key":"e_1_3_3_32_2","first-page":"1342","article-title":"New Ebola outbreak likely sparked by a person infected 5 years ago","volume":"372","author":"Kupferschmidt K.","year":"2021","unstructured":"K. Kupferschmidt, New Ebola outbreak likely sparked by a person infected 5 years ago. Science 372, 1342\u20131344 (2021).","journal-title":"Science"},{"key":"e_1_3_3_33_2","unstructured":"Projet des Fi\u00e8vres H\u00e9morragiques Virales de Guin\u00e9e Release - 4 EBOV genomes from Guinea 2021 outbreak; https:\/\/virological.org\/t\/release-4-ebov-genomes-from-guinea-2021-outbreak\/642."},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03901-9"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13777"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad5224"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy285"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30282-6"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2017.113"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)15012-X"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1086\/520589"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature17180"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-98971-0"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-80-2-355"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2009.02.005"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.08.003"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2007.09.010"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.3390\/v12010092"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2201.151212"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw469"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.55.1.44"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01438-20"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.01.015"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.abi5229","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T17:37:26Z","timestamp":1705426646000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.abi5229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,9]]},"references-count":52,"journal-issue":{"issue":"631","published-print":{"date-parts":[[2022,2,9]]}},"alternative-id":["10.1126\/scitranslmed.abi5229"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.abi5229","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,9]]},"article-number":"eabi5229"}}