Secreted Oral Epithelial Cell Membrane Vesicles Induce Epstein-Barr Virus Reactivation in Latently Infected B Cells

• DOI: 10.1128/jvi.02830-15
• Publication Date: 2016-01-14T09:42:57Z
• Authors: Zhen Lin; Kenneth Swan; Xin Zhang; Subing Cao; Zoe Brett; Stacy Drury; Michael J. Strong; Claire Fewell; Adriane Puetter; Xia Wang; MaryBeth Ferris; Deborah E. Sullivan; Li Li; Erik K. Flemington
• Keywords: Lytic cycle

In the oral epithelium, peripheral stores of Epstein-Barr virus (EBV) are transmitted from infiltrating B cells to epithelial cells. Once is cells, highly permissive nature this cell type for lytic replication allows amplification and exchange other hosts. Since initial transfer EBV requires transitioning B-cell a state that induces reactivation, we hypothesized there might be epithelium-specific signals allow sense appropriate environment initiate reactivation begin process. We previously found miR-200 family microRNAs promotes replication. Here show high levels members in tonsillar epithelia saliva. Analysis cultured (OKF6) showed they actively secrete membrane vesicles (exosomes) enriched with members. Coculturing EBV-positive OKF6 induced viral reactivation. Further, treatment cell-derived promoted Using system does not naturally express members, enforced expression member produced were able induce cascade propose secreted by may serve as tissue-specific environmental cue initiates promoting epithelium facilitate hosts.Epstein-Barr an important human pathogen causally associated several lymphomas carcinomas. The switch latency cycle critical successful host infection pathogenesis. Although can triggered certain agents vitro, mechanisms signal vivo poorly understood. reported endogenously expressed likely play role facilitating tendencies contain proximal where trigger intercellular communication pathway sensor mechanism recognize thereby allowing epithelium.