{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T10:22:34Z","timestamp":1786789354574,"version":"build-2736575974"},"reference-count":117,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T00:00:00Z","timestamp":1569196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"US FDA, The Medical Countermeasures Initiative (MCMi)","award":["OCET 2015916"],"award-info":[{"award-number":["OCET 2015916"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Macrophages are one of the first and also a major site of filovirus replication and, in addition, are a source of multiple cytokines, presumed to play a critical role in the pathogenesis of the viral infection. Some of these cytokines are known to induce macrophage phenotypic changes in vitro, but how macrophage polarization may affect the cell susceptibility to filovirus entry remains largely unstudied. We generated different macrophage subsets using cytokine pre-treatment and subsequently tested their ability to fuse with beta-lactamase containing virus-like particles (VLP), pseudotyped with the surface glycoprotein of Ebola virus (EBOV) or the glycoproteins of other clinically relevant filovirus species. We found that pre-incubation of primary human monocyte-derived macrophages (MDM) with interleukin-10 (IL-10) significantly enhanced filovirus entry into cells obtained from multiple healthy donors, and the IL-10 effect was preserved in the presence of pro-inflammatory cytokines found to be elevated during EBOV disease. In contrast, fusion of IL-10-treated macrophages with influenza hemagglutinin\/neuraminidase pseudotyped VLPs was unchanged or slightly reduced. Importantly, our in vitro data showing enhanced virus entry are consistent with the correlation established between elevated serum IL-10 and increased mortality in filovirus infected patients and also reveal a novel mechanism that may account for the IL-10-mediated increase in filovirus pathogenicity.<\/jats:p>","DOI":"10.3390\/v11100889","type":"journal-article","created":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T11:02:00Z","timestamp":1569236520000},"page":"889","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cytokine Effects on the Entry of Filovirus Envelope Pseudotyped Virus-Like Particles into Primary Human Macrophages"],"prefix":"10.3390","volume":"11","author":[{"given":"Tzanko S.","family":"Stantchev","sequence":"first","affiliation":[{"name":"Division of Biotechnology Review and Research 1 (DBRR1), Office of Biotechnology Products (OBP), Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA), Silver Spring, MD 20993, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Autumn","family":"Zack-Taylor","sequence":"additional","affiliation":[{"name":"Division of Biotechnology Review and Research 1 (DBRR1), Office of Biotechnology Products (OBP), Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA), Silver Spring, MD 20993, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Mattson","sequence":"additional","affiliation":[{"name":"Division of Biotechnology Review and Research 1 (DBRR1), Office of Biotechnology Products (OBP), Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA), Silver Spring, MD 20993, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Strebel","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5382-0510","authenticated-orcid":false,"given":"Christopher C.","family":"Broder","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen A.","family":"Clouse","sequence":"additional","affiliation":[{"name":"Division of Biotechnology Review and Research 1 (DBRR1), Office of Biotechnology Products (OBP), Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA), Silver Spring, MD 20993, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S188","DOI":"10.1086\/514283","article-title":"Markedly elevated levels of interferon (ifn)-gamma, ifn-alpha, interleukin (il)-2, il-10, and tumor necrosis factor-alpha associated with fatal ebola virus infection","volume":"179","author":"Villinger","year":"1999","journal-title":"J. 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