{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T13:30:32Z","timestamp":1775482232505,"version":"3.50.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T00:00:00Z","timestamp":1700092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The nonclassical antigen presentation molecule CD1d presents lipid antigens to invariant natural killer T (iNKT) cells. Activation of these cells triggers a rapid cytokine response providing an interface between innate and adaptive immune responses. The importance of CD1d and iNKT cells in varicella zoster virus (VZV) infection has been emphasized by clinical reports of individuals with CD1d or iNKT cell deficiencies experiencing severe, disseminated varicella postvaccination.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Three strains of VZV (VZV-S, rOka, and VZV rOka-66S) were used to infect Jurkat cells. Flow cytometry of VZV- and mock-infected cells assessed the modulatory impact of VZV on CD1d protein. Infected cell supernatant and transwell co-culture experiments explored the role of soluble factors in VZV-mediated immunomodulation. CD1d transcripts were assessed by reverse-transcription polymerase chain reaction.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Surface and intracellular flow cytometry demonstrated that CD1d was strikingly downregulated by VZV-S and rOka in both infected and VZV antigen-negative cells compared to mock. CD1d downregulation is cell-contact dependent and CD1d transcripts are targeted by VZV. Mechanistic investigations using rOka-66S (unable to express the viral kinase ORF66) implicate this protein in CD1d modulation in infected cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>VZV implements multiple mechanisms targeting both CD1d transcript and protein. This provides evidence of VZV interaction with and manipulation of the CD1d\u2013iNKT cell axis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiad512","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T22:47:26Z","timestamp":1700002046000},"page":"e416-e426","source":"Crossref","is-referenced-by-count":8,"title":["Varicella Zoster Virus Downregulates Expression of the Nonclassical Antigen Presentation Molecule CD1d"],"prefix":"10.1093","volume":"230","author":[{"given":"Renee","family":"Traves","sequence":"first","affiliation":[{"name":"Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney , New South Wales , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tara","family":"Opadchy","sequence":"additional","affiliation":[{"name":"Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney , New South Wales , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry","family":"Slobedman","sequence":"additional","affiliation":[{"name":"Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney , New South Wales , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison","family":"Abendroth","sequence":"additional","affiliation":[{"name":"Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney , New South Wales , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,11,16]]},"reference":[{"key":"2024081523515686600_jiad512-B1","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1084\/jem.20040634","article-title":"Varicella-zoster 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