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In this study, we detected both Epstein\u2013Barr virus (EBV) latency infection genes EBNA\u20101 and LMP\u20101 and EBV lytic infection BZLF\u20101 and BRLF\u20101 expression in the HIC bladders, indicating the coexistence of EBV persistence and reactivation in the B cells in HIC bladders. Upregulation of EBV\u2010associated inflammatory genes in HIC bladders, such as TNF\u2010\u03b1 and IL\u20106, suggests EBV infection is implicated in the pathogenesis of bladder inflammation. Nerve hyperplasia and upregulation of brain\u2010derived neurotrophic factor (BDNF) were noted in the HIC bladders. Double immunochemical staining and flow cytometry revealed the origin of BDNF to be EBV\u2010infected B cells. Inducible BDNF expression was noted in B cells upon EBV infection, but not in the T cells. A chromatin immunoprecipitation study revealed BDNF transcription could be promoted by cooperation between EBV nuclear antigens, chromatin modifiers, and B\u2010cell\u2010specific transcription. Knockdown of BDNF in EBV\u2010infected B cells resulted in the inhibition of cell proliferation and viability. Downregulation of phosphorylated SMAD2 and STAT3 after BDNF knockdown may play a role in the mechanism. Implantation of latent EBV\u2010infected B cells into rat bladder walls resulted in a higher expression level of CD45 and PGP9.5, suggesting tissue inflammation and nerve hyperplasia. In contrast, implantation of BDNF depleted EBV\u2010infected B cells abrogated these effects. This is the first study to provide insights into the mechanisms underlying the involvement of EBV\u2010infected B cells in HIC pathogenesis. \u00a9 2022 The Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.6040","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T10:44:24Z","timestamp":1669632264000},"page":"276-290","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["<scp>EBV<\/scp> infection mediated <scp>BDNF<\/scp> expression is associated with bladder inflammation in interstitial cystitis\/bladder pain syndrome with Hunner's lesion"],"prefix":"10.1002","volume":"259","author":[{"given":"Jia\u2010Fong","family":"Jhang","sequence":"first","affiliation":[{"name":"Department of Urology, Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation  Hualien Taiwan"},{"name":"Department of Urology, School of Medicine Tzu Chi University  Hualien 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