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Until that point, EBV was primarily viewed as a cancer\u2010causing agent, but the culmination of evidence now shows that EBV has a pivotal role in development of MS. Early MS disease is characterised by episodic neuroinflammation and focal lesions in the central nervous system (CNS) that over time develop into progressive neurodegeneration and disability. Risk of MS is vanishingly low in EBV seronegative individuals, history of infectious mononucleosis (acute symptomatic primary infection with EBV) significantly increases risk and elevated antibody titres directed against EBV antigens are well\u2010characterised in patients. However, the underlying mechanism \u2013 or mechanisms \u2013 responsible for this interplay remains to be fully elucidated; how does EBV\u2010induced immune dysregulation either trigger or drive MS in susceptible individuals? Furthermore, deep understanding of virological and immunological events during primary infection and long\u2010term persistence in B cells will help to answer the many questions that remain regarding MS pathogenesis. This review discusses the current evidence and mechanisms surrounding EBV and MS, which have important implications for the future of MS therapies and prevention.<\/jats:p>","DOI":"10.1002\/cti2.1451","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T00:05:21Z","timestamp":1684368321000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["<scp>Epstein\u2013Barr<\/scp> virus and multiple sclerosis: moving from questions of association to questions of mechanism"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2011-1344","authenticated-orcid":false,"given":"Olivia G","family":"Thomas","sequence":"first","affiliation":[{"name":"Department of Clinical Neuroscience, Therapeutic Immune Design, Centre for Molecular Medicine Karolinska Institute  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Rickinson","sequence":"additional","affiliation":[{"name":"Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences University of Birmingham, Edgbaston  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1113-3306","authenticated-orcid":false,"given":"Umaimainthan","family":"Palendira","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, Faculty of Medicine and Health The University of Sydney  Camperdown NSW Australia"},{"name":"Charles Perkins Centre The University of Sydney  Camperdown NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis646"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2018-320189"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2016.187"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410360804"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2009.01291.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(81)91527-0"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21978"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj8222"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005286"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00318-7"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra032015"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2022.105267"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1980.00500510052009"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458512449682"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21117"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458513494489"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.12.7481"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000247665.94088.8d"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.15.1875"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70196-5"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458511408991"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.293.20.2496"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2009.08.004"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2011.42"},{"key":"e_1_2_9_26_1","unstructured":"HuangJ.Biomarkers and viral risk factors in multiple sclerosis. 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