{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T14:04:38Z","timestamp":1787666678839,"version":"build-2736575974"},"reference-count":56,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Multiple sclerosis (MS) constitutes a chronic autoimmune, inflammatory, and neurodegenerative disease, with dissemination in space and time, warranting diagnosis. Epstein\u2013Barr virus (EBV) is increasingly recognized as a key contributor to MS pathogenesis. This review summarizes evidence on EBV-related mechanisms of currently approved disease-modifying therapies (DMTs) and emerging EBV-directed therapeutic strategies in MS. Methods: A systematic search of PubMed, Embase, Cochrane, and Web of Science was performed. Original English-language studies addressing EBV-related therapeutic mechanisms or EBV-targeted interventions in MS were included; 23 studies met the inclusion criteria. Results: Current DMTs may influence EBV-related immunity through diverse mechanisms, including modulation of B-cell subsets, altered lymphocyte trafficking, reduction in EBV-specific humoral responses, and restoration of T-cell surveillance. Monoclonal antibody-based therapies, particularly anti-CD20 agents and natalizumab, appear to affect the EBV\u2013B-cell\u2013immune axis through distinct but complementary mechanisms. Other interventions, including interferons, glatiramer acetate, dimethyl fumarate, autologous hematopoietic stem cell transplantation, and vitamin D supplementation, may also modulate EBV-specific cellular or humoral responses, although the magnitude and durability of these effects vary. Emerging EBV-directed approaches, including EBV-specific T-cell therapy, inhibition of specific proteins, modulation of autophagy, and cholesterol-dependent viral latency, provide additional support for targeting EBV-related pathways in MS. Conclusions: The therapeutic efficacy of DMTs in MS may extend beyond nonspecific immunomodulation and involve partial disruption of EBV-driven immune persistence. Further controlled studies are required to validate EBV-related biomarkers and determine whether direct EBV-targeted therapies can provide sustained clinical benefit.<\/jats:p>","DOI":"10.3390\/jcm15114104","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T11:02:51Z","timestamp":1779793371000},"page":"4104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Experimental Therapies in Multiple Sclerosis: Epstein\u2013Barr Virus and Potential EBV-Related Therapeutic Strategies\u2014A Systematic Review"],"prefix":"10.3390","volume":"15","author":[{"given":"Julia","family":"Bartczak","sequence":"first","affiliation":[{"name":"Department of Neurology, Faculty of Medicine and Dentistry, Medical University of Warsaw, 01-809 Warszawa, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0998-2061","authenticated-orcid":false,"given":"Piotr","family":"Gronowski","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine and Dentistry, Medical University of Warsaw, 01-809 Warszawa, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martyna","family":"Ma\u0142ek","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine and Dentistry, Medical University of Warsaw, 01-809 Warszawa, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Denkiewicz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine and Dentistry, Medical University of Warsaw, 01-809 Warszawa, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4398-675X","authenticated-orcid":false,"given":"Olga","family":"Grodzka","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine and Dentistry, Medical University of Warsaw, 01-809 Warszawa, Poland"},{"name":"Doctoral School, Medical University of Warsaw, 02-091 Warszawa, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8770-5393","authenticated-orcid":false,"given":"Piotr","family":"Ch\u0105dzy\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine and Dentistry, Medical University of Warsaw, 01-809 Warszawa, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3130-1036","authenticated-orcid":false,"given":"Izabela","family":"Domitrz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine and Dentistry, Medical University of Warsaw, 01-809 Warszawa, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1016\/S0140-6736(18)30481-1","article-title":"Multiple sclerosis","volume":"391","author":"Thompson","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/s41572-018-0041-4","article-title":"Multiple sclerosis","volume":"4","author":"Filippi","year":"2018","journal-title":"Nat. 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