Extracellular vesicles from wild-type Epstein–Barr virus–transformed B-cells export host DNA and EBV EBER1
Year: 2026
Type: preprint
Abstract: ABSTRACT Epstein–Barr virus (EBV) infection is nearly ubiquitous and strongly linked to multiple sclerosis (MS), but how EBV-infected B cells communicate with distal tissues remains unclear. 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 ex vivo by endogenous wild-type EBV. Proteomics identified over 6,000 shared proteins enriched in nucleic acid–binding and chromatin-associated factors. EV-associated DNA resolved into two structurally distinct compartments: DNase-sensitive, high–molecular weight DNA associated with the vesicle corona and DNase-resistant, nucleosome-sized (∼130–150 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.
Authors: Michelle L. Pleet, Rose Peterson, Stephanie Chidester, Emily H. Stack, Madeleine R. Druker, Jubin George, Charlotte V. Dagli, Abaigeal Donaldson, Joanna Palade, Elizabeth Hutchins, Chang-Sook Hong, Nyater Ngouth, Joan Ohayon, Maria Chiara Monaco, Jason Savage, Tapan K. Maity, Weiming Yang, Lisa M. Jenkins, Ru-Ching Hsia, Ionita C. Ghiran, Kendall van Keuren-Jensen, Kory Johnson, Jennifer C. Jones, Steven Jacobson
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G5923571890, Immunologic Mechanisms In Experimental Autoimmune Diseases Of The Nervous System, G9000184186, Discovery of Tumor, Treatment Response, and Systems-based EVP Signatures, Extracellular Vesicle Hallmarks of Viral Malignancies, Involvement Of Human Viruses Associated With Chronic Neurologic Disease
OpenAlex ID: W7147181665
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