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We hypothesize that, during malaria onset, the reactivated EBV can infect human brain microvascular endothelial cells (HBECs). This may cause severe cerebral manifestations. We infected HBECs with EBV in vitro. The subsequent gene expression pattern of EBV, inflammatory and endothelial markers was analysed using qRT-PCR. Further, a wound-healing assay for cells maintaining blood\u2013brain barrier (BBB) integrity was performed to investigate the effect of EBV-infected HBECs secretions. The RBC adhesion assay was conducted to assess RBC attachment onto HBECs during EBV and P. falciparum mono- and co-infection. Our experiments revealed that EBV infection of HBECs significantly elevated several inflammatory (TNF\u03b1, CCL2) and endothelial (integrin \u03b23, PECAM, VEGFA, VWF, claudin-5, cx37) markers. The EBV-infected HBECs secretion significantly reduced migration of HBECs, glial and neuronal cells. Additionally, EBV\u2013P. falciparum co-infection significantly (P\u00a0&amp;lt;\u00a00.05) enhanced RBC adhesion to HBECs compared to mono-infection scenarios. Conclusively, the EBV infection of HBECs led to endothelial activation and modulated the BBB microenvironment. The EBV-P. falciparum co-infection scenario increased RBC adhesion on ECs which is a hallmark of cerebral malaria. Together with malaria, EBV infection can aid in exacerbation of cerebral malaria pathology.<\/jats:p>","DOI":"10.1093\/femspd\/ftaa080","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T12:10:10Z","timestamp":1608552610000},"source":"Crossref","is-referenced-by-count":37,"title":["Epstein\u2013Barr virus infection modulates blood\u2013brain barrier cells and its co-infection with <i>Plasmodium falciparum<\/i> induces RBC adhesion"],"prefix":"10.1093","volume":"79","author":[{"given":"Omkar","family":"Indari","sequence":"first","affiliation":[{"name":"Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore 453552, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Chandramohanadas","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, National University of Singapore, Singapore 117545, 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