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However, the exact mechanism by which EBV, specifically in IM, increases the risk for MS remains unknown. EBV immortalizes primary B lymphocytes in vitro and causes excessive B lymphocyte proliferation in IM in vivo. In asymptomatic carriers, EBV\u2010infected B lymphocytes still proliferate to certain degrees, the process of which is tightly controlled by the host immune systems. Experimental autoimmune encephalomyelitis (EAE) mimics key features of MS in humans and is a well\u2010established rodent model for human MS. We have found that xenografts of EBV\u2010immortalized B lymphocytes, which partially resemble the hyperproliferation of EBV\u2010infected cells in IM, exacerbate autoimmune responses in myelin oligodendrocyte glycoprotein\u2010induced EAE in C57BL\/6 mice. After remission, an additional challenge with EBV\u2010immortalized cells induces a relapse in EAE. Moreover, xenografts with EBV\u2010immortalized cells tighten the integrity of the blood\u2010brain barrier (BBB) in the thalamus and hypothalamus areas of the mouse brains. Genomic sequences of prokaryotic 16S ribosomal RNA presented in the feces reveal that EBV\u2010immortalized cells significantly change the diversities of microbial populations. Our data collectively suggest that EBV\u2010mediated proliferation of B lymphocytes may be a risk factor for the exacerbation of MS, which are associated with gut microbiome changes and BBB modulations. Furthermore, multiple xenografts of EBV\u2010immortalized cells into C57BL\/6 mice could serve as a useful model for human relapsing\u2010remitting MS with predictable severity and timing.<\/jats:p>","DOI":"10.1002\/jmv.26188","type":"journal-article","created":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T14:21:38Z","timestamp":1592317298000},"page":"3813-3823","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Epstein\u2010Barr virus\u2010immortalized B lymphocytes exacerbate experimental autoimmune encephalomyelitis in xenograft mice"],"prefix":"10.1002","volume":"93","author":[{"given":"Pascal","family":"Polepole","sequence":"first","affiliation":[{"name":"Nebraska Center for Virology University of Nebraska Lincoln Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Bartenslager","sequence":"additional","affiliation":[{"name":"Department of Animal Science University 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