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We performed an integrated multiomic characterization of small extracellular vesicles (sEVs) released from spontaneous lymphoblastoid cell lines (SLCLs) derived from healthy donors and patients with MS, transformed\n                  <jats:italic>ex vivo<\/jats:italic>\n                  by endogenous wild-type EBV. Proteomics identified over 6,000 shared proteins enriched in nucleic acid\u2013binding and chromatin-associated factors. EV-associated DNA resolved into two structurally distinct compartments: DNase-sensitive, high\u2013molecular weight DNA associated with the vesicle corona and DNase-resistant, nucleosome-sized (\u223c130\u2013150 bp) DNA. Both compartments were overwhelmingly host-derived and broadly genomically distributed, whereas EBV DNA was minimal. In contrast, viral RNA cargo was dominated by the EBV noncoding RNA EBER1, which was strikingly enriched across all lines and confirmed within individual vesicles by ddPCR and super-resolution microscopy. EBER1 has previously been detected in MS brain tissue, yet its route to the CNS has remained unexplained. Our findings identify sEVs as a plausible vehicle for disseminating this immunostimulatory viral ncRNA beyond sites of latency, pointing to EV-mediated export of EBER1 as a candidate mechanism linking peripheral EBV infection to distal tissue signaling in MS and beyond.\n                <\/jats:p>","DOI":"10.64898\/2026.03.30.715356","type":"posted-content","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T12:45:13Z","timestamp":1775047513000},"source":"Crossref","is-referenced-by-count":0,"title":["Extracellular vesicles from wild-type Epstein\u2013Barr virus\u2013transformed B-cells export host DNA and EBV EBER1"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0102-711X","authenticated-orcid":false,"given":"Michelle L.","family":"Pleet","sequence":"first","affiliation":[{"name":"Translational Nanobiology Section, Laboratory of Pathology, Center for Cancer Research, NCI\/NIH, Bethesda, MD, USA"},{"name":"Viral Immunology Section, Neuroimmunology 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