{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:05:45Z","timestamp":1792789545453,"version":"4.5.0"},"reference-count":51,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T00:00:00Z","timestamp":1683849600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"BU Hariri Pilot Research award"},{"name":"NIH Shared Instrument","award":["S10-OD026983"],"award-info":[{"award-number":["S10-OD026983"]}]},{"name":"NIH Shared Instrument","award":["S10-OD030269"],"award-info":[{"award-number":["S10-OD030269"]}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["HHSN272201800013C"],"award-info":[{"award-number":["HHSN272201800013C"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Vet Pathol"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:p>\n                    The liver is an early systemic target of Ebola virus (EBOV), but characterization beyond routine histopathology and viral antigen distribution is limited. We hypothesized Ebola virus disease (EVD) systemic proinflammatory responses would be reflected in temporally altered liver myeloid phenotypes. We utilized multiplex fluorescent immunohistochemistry (mfIHC), multispectral whole slide imaging, and image analysis to quantify molecular phenotypes of myeloid cells in the liver of rhesus macaques ( Macaca mulatta; n = 21) infected with EBOV Kikwit. Liver samples included uninfected controls ( n = 3), 3 days postinoculation (DPI; n = 3), 4 DPI ( n = 3), 5 DPI ( n = 3), 6 DPI ( n = 3), and terminal disease (6\u20138 DPI; n = 6). Alterations in hepatic macrophages occurred at \u2265 5 DPI characterized by a 1.4-fold increase in CD68+ immunoreactivity and a transition from primarily CD14\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD16\n                    <jats:sup>+<\/jats:sup>\n                    to CD14\n                    <jats:sup>+<\/jats:sup>\n                    CD16\n                    <jats:sup>\u2212<\/jats:sup>\n                    macrophages, with a 2.1-fold decrease in CD163 expression in terminal animals compared with uninfected controls. An increase in the neutrophil chemoattractant and alarmin S100A9 occurred within hepatic myeloid cells at 5 DPI, followed by rapid neutrophil influx at \u2265 6 DPI. An acute rise in the antiviral myxovirus resistance protein 1 (MxA) occurred at \u2265 4 DPI, with a predilection for enhanced expression in uninfected cells. Distinctive expression of major histocompatibility complex (MHC) class II was observed in hepatocytes during terminal disease. Results illustrate that EBOV causes macrophage phenotype alterations as well as neutrophil influx and prominent activation of interferon host responses in the liver. Results offer insight into potential therapeutic strategies to prevent and\/or modulate the host proinflammatory response to normalize hepatic myeloid functionality.\n                  <\/jats:p>","DOI":"10.1177\/03009858231171906","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T06:05:17Z","timestamp":1683871517000},"page":"473-487","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Hepatic proinflammatory myeloid phenotypes are a hallmark of Ebola virus Kikwit pathogenesis in rhesus monkeys"],"prefix":"10.1177","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4791-374X","authenticated-orcid":false,"given":"Anna E.","family":"Tseng","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA"},{"name":"National Emerging Infectious Diseases Laboratories, NEIDL Comparative Pathology Laboratory, Boston University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3864-5915","authenticated-orcid":false,"given":"Mariano","family":"Carossino","sequence":"additional","affiliation":[{"name":"Louisiana Animal Disease Diagnostic Laboratory (LADDL), Louisiana State University, Baton Rouge, LA, USA"},{"name":"Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans P.","family":"Gertje","sequence":"additional","affiliation":[{"name":"National Emerging Infectious Diseases Laboratories, NEIDL Comparative Pathology Laboratory, Boston University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoife K.","family":"O\u2019Connell","sequence":"additional","affiliation":[{"name":"National Emerging Infectious Diseases Laboratories, NEIDL Comparative Pathology Laboratory, Boston University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suryaram","family":"Gummuluru","sequence":"additional","affiliation":[{"name":"National Emerging Infectious Diseases Laboratories, NEIDL Comparative Pathology Laboratory, Boston University, Boston, MA, USA"},{"name":"Department of Microbiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijaya B","family":"Kolachalama","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA"},{"name":"Department of Computer Science, Boston University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udeni B. R.","family":"Balasuriya","sequence":"additional","affiliation":[{"name":"Louisiana Animal Disease Diagnostic Laboratory (LADDL), Louisiana State University, Baton Rouge, LA, USA"},{"name":"Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Connor","sequence":"additional","affiliation":[{"name":"National Emerging Infectious Diseases Laboratories, NEIDL Comparative Pathology Laboratory, Boston University, Boston, MA, USA"},{"name":"Department of Microbiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Integrated Research Facility, National Institute for Allergy and Infectious Diseases (NIAID), Frederick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David X.","family":"Liu","sequence":"additional","affiliation":[{"name":"Integrated Research Facility, National Institute for Allergy and Infectious Diseases (NIAID), Frederick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa E.","family":"Hensley","sequence":"additional","affiliation":[{"name":"Integrated Research Facility, National Institute for Allergy and Infectious Diseases (NIAID), Frederick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3873-9188","authenticated-orcid":false,"given":"Nicholas A.","family":"Crossland","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA"},{"name":"National Emerging Infectious Diseases Laboratories, NEIDL Comparative Pathology Laboratory, Boston University, 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