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Clinical MS onset occurs years after primary EBV infection and the mechanisms linking them remain largely unclear. This review summarizes the epidemiological evidence for this association and how the EBV specific immune control is altered in MS patients. The two main possibilities of mechanisms for this association are further discussed. Firstly, immune responses that are induced during a symptomatic primary EBV infection, namely infectious mononucleosis, might be amplified during the following years to finally cause central nervous system (CNS) inflammation and demyelination. Secondly, genetic predisposition and environmental factors might not allow for an efficient immune control of the EBV-infected B cells that might drive autoimmune T cell stimulation or CNS inflammation. These two main hypotheses for explaining the association of the EBV with MS would implicate opposite therapeutic interventions, namely either dampening CNS inflammatory EBV-reactive immune responses or strengthening them to eliminate the autoimmunity stimulating EBV-infected B cell compartment. Nevertheless, recent findings suggest that EBV is an important puzzle piece in the pathogenesis of MS, and understanding its contribution could open new treatment possibilities for this autoimmune disease.<\/jats:p>","DOI":"10.3390\/cells11172757","type":"journal-article","created":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T20:48:25Z","timestamp":1662410905000},"page":"2757","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Altered Immune Response to the Epstein\u2013Barr Virus as a Prerequisite for Multiple Sclerosis"],"prefix":"10.3390","volume":"11","author":[{"given":"Fabienne","family":"L\u00e4derach","sequence":"first","affiliation":[{"name":"Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6419-1940","authenticated-orcid":false,"given":"Christian","family":"M\u00fcnz","sequence":"additional","affiliation":[{"name":"Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/s41579-019-0249-7","article-title":"Latency and lytic replication in the oncogenesis of the Epstein Barr virus","volume":"17","year":"2019","journal-title":"Nat. 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