{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T09:29:15Z","timestamp":1780824555236,"version":"3.54.1"},"reference-count":87,"publisher":"American Society for Clinical Investigation","issue":"16","license":[{"start":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T00:00:00Z","timestamp":1661126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cincinnati Children\u2019s Research Foundation, Cincinnati, OH.","award":["53512-589000-32-143083-001"],"award-info":[{"award-number":["53512-589000-32-143083-001"]}]},{"DOI":"10.13039\/100010327","name":"Cincinnati Children\u2019s Research Foundation","doi-asserted-by":"crossref","award":["53512-589000-32-143083-001"],"award-info":[{"award-number":["53512-589000-32-143083-001"]}],"id":[{"id":"10.13039\/100010327","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,22]]},"abstract":"<jats:p>\n                    Accumulation of activated natural killer (NK) cells in tissues during Ebola virus infection contributes to Ebola virus disease (EVD) pathogenesis. Yet, immunization with Ebola virus-like particles (VLPs) comprising glycoprotein and matrix protein VP40 provides rapid, NK cell\u2013mediated protection against Ebola challenge. We used Ebola VLPs as the viral surrogates to elucidate the molecular mechanism by which Ebola virus triggers heightened NK cell activity. Incubation of human peripheral blood mononuclear cells with Ebola VLPs or VP40 protein led to increased expression of IFN-\u03b3, TNF-\u03b1, granzyme B, and perforin by CD3\n                    <jats:sup>\u2013<\/jats:sup>\n                    CD56\n                    <jats:sup>+<\/jats:sup>\n                    NK cells, along with increases in degranulation and cytotoxic activity of these cells. Optimal activation required accessory cells like CD14\n                    <jats:sup>+<\/jats:sup>\n                    myeloid and CD14\n                    <jats:sup>\u2013<\/jats:sup>\n                    cells and triggered increased secretion of numerous inflammatory cytokines. VP40-induced IFN-\u03b3 and TNF-\u03b1 secretion by NK cells was dependent on IL-12 and IL-18 and suppressed by IL-10. In contrast, their increased degranulation was dependent on IL-12 with little influence of IL-18 or IL-10. These results demonstrate that Ebola VP40 stimulates NK cell functions in an IL-12\u2013 and IL-18\u2013dependent manner that involves CD14\n                    <jats:sup>+<\/jats:sup>\n                    and CD14\n                    <jats:sup>\u2013<\/jats:sup>\n                    accessory cells. These potentially novel findings may help in designing improved intervention strategies required to control viral transmission during Ebola outbreaks.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.158902","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T12:00:35Z","timestamp":1658404835000},"source":"Crossref","is-referenced-by-count":14,"title":["Ebola virus protein VP40 stimulates IL-12\u2013 and IL-18\u2013dependent activation of human natural killer cells"],"prefix":"10.1172","volume":"7","author":[{"given":"Hung","family":"Le","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5393-9511","authenticated-orcid":true,"given":"Paul","family":"Spearman","sequence":"additional","affiliation":[{"name":"Division of 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