{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T16:33:20Z","timestamp":1777912400315,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012581","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000}}],"reference-count":96,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T00:00:00Z","timestamp":1727308800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004088","name":"Life Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004088","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Friends of HZI"},{"DOI":"10.13039\/501100001656","name":"Helmholtz-Gemeinschaft","doi-asserted-by":"publisher","award":["W2\/W3-090"],"award-info":[{"award-number":["W2\/W3-090"]}],"id":[{"id":"10.13039\/501100001656","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["431451204"],"award-info":[{"award-number":["431451204"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC 2155, grant no 390874280"],"award-info":[{"award-number":["EXC 2155, grant no 390874280"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BMBF","award":["01KI2013"],"award-info":[{"award-number":["01KI2013"]}]},{"name":"BMBF","award":["01KI2013"],"award-info":[{"award-number":["01KI2013"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Epigenetic mechanisms stabilize gene expression patterns during CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell differentiation. Although adoptive transfer of virus-specific T cells is clinically applied to reduce the risk of virus infection or reactivation in immunocompromised individuals, the DNA methylation pattern of virus-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells is largely unknown. Hence, we here performed whole-genome bisulfite sequencing of cytomegalovirus-specific human CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and found that they display a unique DNA methylation pattern consisting of 79 differentially methylated regions (DMRs) when compared to memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Among the top demethylated DMRs in cytomegalovirus-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells was\n                    <jats:italic>TBKBP1<\/jats:italic>\n                    , coding for TBK-binding protein 1 that can interact with TANK-binding kinase 1 (TBK1) and mediate pro-inflammatory responses in innate immune cells downstream of intracellular virus sensing. Since TBKBP1 has not yet been reported in T cells, we aimed to unravel its role in virus-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells.\n                    <jats:italic>TBKBP1<\/jats:italic>\n                    demethylation in terminal effector CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells correlated with higher\n                    <jats:italic>TBKBP1<\/jats:italic>\n                    expression at both mRNA and protein level, independent of alternative splicing of\n                    <jats:italic>TBKBP1<\/jats:italic>\n                    transcripts. Notably, the distinct DNA methylation patterns in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell subsets was stable upon long-term\n                    <jats:italic>in vitro<\/jats:italic>\n                    culture. TBKBP1 overexpression resulted in enhanced TBK1 phosphorylation upon stimulation of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and significantly improved their virus neutralization capacity. Collectively, our data demonstrate that TBKBP1 modulates virus-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses and could be exploited as therapeutic target to improve adoptive T cell therapies.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1012581","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T13:45:23Z","timestamp":1727358323000},"page":"e1012581","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["DNA methylation profiling identifies TBKBP1 as potent amplifier of cytotoxic activity in CMV-specific human CD8+ T cells"],"prefix":"10.1371","volume":"20","author":[{"given":"Zheng","family":"Yu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varun","family":"Sasidharan-Nair","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thalea","family":"Buchta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnes","family":"Bonifacius","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fawad","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beate","family":"Pietzsch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hosein","family":"Ahmadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Beckstette","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"Niemz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Hilgendorf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Mausberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Keller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Falk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk 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M.","family":"Brinkmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Britta","family":"Eiz-Vesper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Floess","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8071-1379","authenticated-orcid":true,"given":"Jochen","family":"Huehn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,9,26]]},"reference":[{"issue":"12","key":"ppat.1012581.ref001","doi-asserted-by":"crossref","first-page":"3881","DOI":"10.4049\/jimmunol.1800171","article-title":"Cytomegalovirus: shape-shifting the immune system","volume":"200","author":"G Picarda","year":"2018","journal-title":"J 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