{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:27:06Z","timestamp":1792153626971,"version":"4.4.0"},"reference-count":59,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"858","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01AI153068-03"],"award-info":[{"award-number":["5R01AI153068-03"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["FG-2207-39811"],"award-info":[{"award-number":["FG-2207-39811"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union\u2019s Horizon Europe Research and Innovation Actions","award":["101136991"],"award-info":[{"award-number":["101136991"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"<jats:p>\n                    Multiple sclerosis (MS) pathogenesis is linked to Epstein-Barr virus (EBV), but the underlying immune mechanisms remain unclear. Using an optimized T cell assay, we demonstrate that CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells from individuals with MS predominantly target EBV viral particle components, specifically the late lytic capsid and glycoprotein antigens, rather than latent antigens. In contrast, the Epstein-Barr nuclear antigen 1 (EBNA1) primarily activated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. EBV-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses were twofold higher in individuals with untreated MS compared with healthy controls, whereas responses to other herpesviruses remained similar. Anti-CD20 therapy initiation in treatment-na\u00efve participants reduced these responses, a finding validated in an independent cohort, and eliminated viral shedding in saliva. Our results establish preferential CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell reactivity to EBV late lytic antigens as a key feature of MS, providing a framework for developing EBV-targeted therapies, including vaccines and antivirals.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adz6566","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T17:59:07Z","timestamp":1784138347000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":9,"title":["CD4\n                    <sup>+<\/sup>\n                    T cells reactive to Epstein-Barr virus late lytic antigens are enriched in individuals with multiple sclerosis"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2892-6986","authenticated-orcid":true,"given":"Kjetil","family":"Bjornevik","sequence":"first","affiliation":[{"name":"Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA."},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0700-3517","authenticated-orcid":true,"given":"Jo\u00e3o Vitor","family":"Mahler","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2672-554X","authenticated-orcid":true,"given":"Philippe A.","family":"Bilodeau","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2200-1525","authenticated-orcid":true,"given":"Brit Ellen","family":"R\u00f8d","sequence":"additional","affiliation":[{"name":"Neuro-SysMed, Department of Neurology, Haukeland University Hospital, Bergen 5021, Norway."},{"name":"Department of Clinical Medicine, University of Bergen, Bergen 5020, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3656-9851","authenticated-orcid":true,"given":"Gabriela","family":"Romanow","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1851-5259","authenticated-orcid":true,"given":"Takahisa","family":"Mikami","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7713-2878","authenticated-orcid":true,"given":"Monique","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6946-3711","authenticated-orcid":true,"given":"Natasha","family":"Bobrowski-Khoury","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4340-1125","authenticated-orcid":true,"given":"Huimin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Matiello","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Housman","sequence":"additional","affiliation":[{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bardia","family":"Nourbakhsh","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0980-510X","authenticated-orcid":true,"given":"Kjell-Morten","family":"Myhr","sequence":"additional","affiliation":[{"name":"Neuro-SysMed, Department of Neurology, Haukeland University Hospital, Bergen 5021, Norway."},{"name":"Department of Clinical Medicine, University of Bergen, Bergen 5020, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5294-2866","authenticated-orcid":true,"given":"\u00d8ivind","family":"Torkildsen","sequence":"additional","affiliation":[{"name":"Neuro-SysMed, Department of Neurology, Haukeland University Hospital, Bergen 5021, Norway."},{"name":"Department of Clinical 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