{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:18:12Z","timestamp":1790050692092,"version":"4.0.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"7","funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Chronic active Epstein-Barr virus (CAEBV) presents with high levels of viral genomes in blood and tissue infiltration with Epstein-Barr virus (EBV)\u2013positive lymphocytes. The pathogenesis of CAEBV is poorly understood.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We evaluated 2 patients with natural killer (NK) cell CAEBV and studied their NK cell phenotype and signaling pathways in cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Both patients had increased numbers of NK cells, EBV predominantly in NK cells, and immature NK cells in the blood. Both patients had increased phosphorylation of Akt, S6, and STAT1 in NK cells, and increased total STAT1. Treatment of 1 patient with sirolimus reduced phosphorylation of S6 in T and B cells, but not in NK cells and did not reduce levels of NK cells or EBV DNA in the blood. Treatment of both patients\u2019 cells with JAK inhibitors in vitro reduced phosphorylated STAT1 to normal. Patients with T- or B-cell CAEBV had increased phosphorylation of Akt and S6 in NK cells, but no increase in total STAT1.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The increase in phosphorylated Akt, S6, and STAT1, as well as immature NK cells describe a new phenotype for NK cell CAEBV. The reduction of STAT1 phosphorylation in their NK cells with JAK inhibitors suggests a novel approach to therapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiaa232","type":"journal-article","created":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T11:11:45Z","timestamp":1588763505000},"page":"1170-1179","source":"Crossref","is-referenced-by-count":12,"title":["Patients With Natural Killer (NK) Cell Chronic Active Epstein-Barr Virus Have Immature NK Cells and Hyperactivation of PI3K\/Akt\/mTOR and STAT1 Pathways"],"prefix":"10.1093","volume":"222","author":[{"given":"Matthew K","family":"Howe","sequence":"first","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kennichi","family":"Dowdell","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Sun","family":"Kuehn","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingxue","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey T","family":"Hart","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doreen","family":"Garabedian","sequence":"additional","affiliation":[{"name":"Leidos Biomedical Research, Inc, Frederick National Laboratory, Frederick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Liepshutz","sequence":"additional","affiliation":[{"name":"Leidos Biomedical Research, Inc, Frederick National Laboratory, Frederick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy P","family":"Hsu","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Su","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Shereck","sequence":"additional","affiliation":[{"name":"Doembecker Children\u2019s Hospital, Oregon Health and Science University, Portland, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Schulz","sequence":"additional","affiliation":[{"name":"Pediatric Hematology and Oncology, Providence Alaska Medical Center, Anchorage, Alaska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana","family":"Feldman","sequence":"additional","affiliation":[{"name":"John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio D","family":"Rosenzweig","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric O","family":"Long","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesia","family":"Dropulic","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey I","family":"Cohen","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 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