{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T12:31:49Z","timestamp":1786624309491,"version":"build-2736575974"},"reference-count":121,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by immune-mediated demyelination and neurodegeneration. Although the exact cause of MS remains unclear, accumulating epidemiological and immunological evidence strongly implicates Epstein\u2013Barr virus (EBV) infection as a major environmental factor associated with disease development. Nearly all individuals with MS are EBV seropositive, and longitudinal studies have demonstrated that EBV infection precedes MS onset, supporting a causal relationship. EBV establishes lifelong latency in B cells and can profoundly influence host immune responses, providing several potential mechanisms through which it may contribute to autoimmunity. In this review, we summarize current knowledge of EBV biology and discuss epidemiological findings linking EBV infection with MS risk. We then examine alterations in EBV-specific immune responses observed in MS, including dysregulated humoral and cellular immunity. Particular attention is given to molecular mimicry involving the Epstein\u2013Barr nuclear antigen 1 (EBNA1) and central nervous system proteins, which may promote cross-reactive autoimmune responses. Finally, we discuss evidence for the presence and potential role of EBV-infected immune cells within the MS brain and highlight key unanswered questions that remain critical for understanding EBV-driven neuroinflammation.<\/jats:p>","DOI":"10.3390\/microorganisms14081639","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T11:54:26Z","timestamp":1785153266000},"page":"1639","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Epstein\u2013Barr Virus and Multiple Sclerosis: Mechanistic Insights into Virus-Driven Autoimmunity"],"prefix":"10.3390","volume":"14","author":[{"given":"Stavros","family":"Bashiardes","sequence":"first","affiliation":[{"name":"Postgraduate School, Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus"},{"name":"Department of Molecular Virology, Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5011-5469","authenticated-orcid":false,"given":"George","family":"Krashias","sequence":"additional","affiliation":[{"name":"Postgraduate School, Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus"},{"name":"Department of Molecular Virology, Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elissa","family":"Englezou","sequence":"additional","affiliation":[{"name":"Postgraduate School, Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus"},{"name":"Department of Molecular Virology, Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Lambrianides","sequence":"additional","affiliation":[{"name":"Postgraduate School, Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus"},{"name":"Department of Neuroimmunology, Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8606-0421","authenticated-orcid":false,"given":"Giorgos","family":"Pitsas","sequence":"additional","affiliation":[{"name":"Neurology Clinic, Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2937-384X","authenticated-orcid":false,"given":"Marios","family":"Pantzaris","sequence":"additional","affiliation":[{"name":"Postgraduate School, Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus"},{"name":"Department of Neuroimmunology, Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3737-7664","authenticated-orcid":false,"given":"Jan","family":"Richter","sequence":"additional","affiliation":[{"name":"Postgraduate School, Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus"},{"name":"Department of Molecular Virology, Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0140-6736(23)01473-3","article-title":"Multiple Sclerosis","volume":"403","author":"Jakimovski","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a028936","DOI":"10.1101\/cshperspect.a028936","article-title":"Multiple Sclerosis Pathology","volume":"8","author":"Lassmann","year":"2018","journal-title":"Cold Spring Harb. 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