{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:39:20Z","timestamp":1772138360048,"version":"3.50.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T00:00:00Z","timestamp":1695945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS116278"],"award-info":[{"award-number":["R01 NS116278"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML), a potentially fatal complication of severe immune suppression with no effective treatment. Natural killer (NK) cells play critical roles in defense against viral infections; however, NK-cell response to JCPyV infection remains unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>NK- and T-cell responses against the JCPyV VP1 were compared using intracellular cytokine staining upon stimulation with peptide pools. A novel flow cytometry-based assay was developed to determine NK-cell killing efficiency of JCPyV-infected astrocyte-derived SVG-A cells. Blocking antibodies were used to evaluate the contribution of NK-cell receptors in immune recognition of JCPyV-infected cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In about 40% of healthy donors, we detected robust CD107a upregulation and IFN-\u03b3 production by NK cells, extending beyond T-cell responses. Next, using the NK-cell\u2013mediated killing assay, we showed that coculture of NK cells and JCPyV-infected SVG-A cells leads to a 60% reduction in infection, on average. JCPyV-infected cells had enhanced expression of ULBP2\u2014a ligand for the activating NK-cell receptor NKG2D, and addition of NKG2D blocking antibodies decreased NK-cell degranulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>NKG2D-mediated activation of NK cells plays a key role in controlling JCPyV replication and may be a promising immunotherapeutic target to boost NK-cell anti-JCPyV activity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiad424","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T16:20:52Z","timestamp":1695918052000},"page":"1836-1844","source":"Crossref","is-referenced-by-count":3,"title":["Upregulation of the NKG2D Ligand ULBP2 by JC Polyomavirus Infection Promotes Immune Recognition by Natural Killer Cells"],"prefix":"10.1093","volume":"229","author":[{"given":"Stephanie","family":"Jost","sequence":"first","affiliation":[{"name":"Division of Innate and Comparative Immunology, Center for Human Systems Immunology, Department of Surgery, Duke University School of Medicine , Durham, North Carolina , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny","family":"Ahn","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts , 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