{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:47:53Z","timestamp":1790365673038,"version":"4.1.0"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,3,9]],"date-time":"2019-03-09T00:00:00Z","timestamp":1552089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT 361426"],"award-info":[{"award-number":["PJT 361426"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008220","name":"Canadian Foundation for AIDS Research","doi-asserted-by":"publisher","award":["28-509"],"award-info":[{"award-number":["28-509"]}],"id":[{"id":"10.13039\/100008220","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Expansion of natural killer (NK) cells expressing NKG2C occurs following human cytomegalovirus (HCMV) infection and is amplified by human immunodeficiency virus (HIV) co-infection. These NKG2C-expressing NK cells demonstrate enhanced CD16-dependent cytokine production and downregulate Fc\u03b5RI\u03b3 and promyelocytic leukemia zinc finger protein (PLZF). Lacking NKG2C diminishes resistance to HIV infection, but whether this affects NK cell acquisition of superior antibody-dependent function is unclear. Therefore, our objective was to investigate whether HCMV-driven NK cell differentiation is impaired in NKG2Cnull HIV-infected individuals. Phenotypic (CD2, CD16, CD57, NKG2A, Fc\u03b5RI\u03b3, and PLZF expression) and functional (cytokine induction and cytotoxicity) properties were compared between HIV\u2013infected NKG2Cnull and NKG2C-expressing groups. Cytokine production was compared following stimulation through natural cytotoxicity receptors or through CD16. Cytotoxicity was measured by anti-CD16-redirected lysis and by classical antibody-dependent cell-mediated cytotoxicity (ADCC) against anti-class I human leukocyte antigen (HLA) antibody-coated cells. Our data indicate highly similar HCMV-driven NK cell differentiation in HIV infection with or without NKG2C. While the fraction of mature (CD57pos) NK cells expressing CD2 (p = 0.009) or co-expressing CD2 and CD16 (p = 0.03) was significantly higher in NKG2Cnull HIV-infected individuals, there were no significant differences in NKG2A, Fc\u03b5RI\u03b3, or PLZF expression. The general phenotypic and functional equivalency observed suggests NKG2C-independent routes of HCMV-driven NK cell differentiation, which may involve increased CD2 expression.<\/jats:p>","DOI":"10.3390\/v11030239","type":"journal-article","created":{"date-parts":[[2019,3,12]],"date-time":"2019-03-12T03:49:31Z","timestamp":1552362571000},"page":"239","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Cytomegalovirus-Driven Adaption of Natural Killer Cells in NKG2Cnull Human Immunodeficiency Virus-Infected Individuals"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6713-5378","authenticated-orcid":false,"given":"Emilie M.","family":"Comeau","sequence":"first","affiliation":[{"name":"Immunology and Infectious Diseases Program, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philp Drive, St. John\u2019s, NL A1B 3V6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1544-067X","authenticated-orcid":false,"given":"Kayla A.","family":"Holder","sequence":"additional","affiliation":[{"name":"Immunology and Infectious Diseases Program, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philp Drive, St. John\u2019s, NL A1B 3V6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neva J.","family":"Fudge","sequence":"additional","affiliation":[{"name":"Immunology and Infectious Diseases Program, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philp Drive, St. John\u2019s, NL A1B 3V6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0377-2036","authenticated-orcid":false,"given":"Michael D.","family":"Grant","sequence":"additional","affiliation":[{"name":"Immunology and Infectious Diseases Program, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philp Drive, St. John\u2019s, NL A1B 3V6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/infdis\/151.5.772","article-title":"Cytomegaloviral infection and disease","volume":"151","author":"Kinney","year":"1985","journal-title":"J. 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