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The Role of Transforming Growth Factor β in Cell-to-Cell Contact-Mediated Epstein-Barr Virus Transmission

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/70996

Title: The Role of Transforming Growth Factor β in Cell-to-Cell Contact-Mediated Epstein-Barr Virus Transmission
Authors: Nanbo, Asuka Browse this author →KAKEN DB
Ohashi, Makoto Browse this author
Yoshiyama, Hironori Browse this author →KAKEN DB
Ohba, Yusuke Browse this author →KAKEN DB
Keywords: Epstein-Barr virus
cell-to-cell contact-mediated transmission
viral replication
TGF-β
exosomes
Issue Date: 15-May-2018
Publisher: Frontiers Media
Journal Title: Frontiers in microbiology
Volume: 9
Start Page: 984
Publisher DOI: 10.3389/fmicb.2018.00984
Abstract: Infection of Epstein-Barr virus (EBV), a ubiquitous human gamma herpesvirus, is closely linked to various lymphoid and epithelial malignancies. Previous studies demonstrated that the efficiency of EBV infection in epithelial cells is significantly enhanced by coculturing them with latently infected B cells relative to cell-free infection, suggesting that cell-to-cell contact-mediated viral transmission is the dominant mode of infection by EBV in epithelial cells. However, a detailed mechanism underlying this process has not been fully understood. In the present study, we assessed the role of transforming growth factor β (TGF-β), which is known to induce EBV's lytic cycle by upregulation of EBV's latent-lytic switch BZLF1 gene. We have found that 5 days of cocultivation facilitated cell-to-cell contact-mediated EBV transmission. Replication of EBV was induced in cocultured B cells both with and without a direct cell contact in a time-dependent manner. Treatment of a blocking antibody for TGF-β suppressed both induction of the lytic cycle in cocultured B cells and subsequent viral transmission. Cocultivation with epithelial cells facilitated expression of TGF-β receptors in B cells and increased their susceptibility to TGF-β. Finally, we confirmed the spontaneous secretion of TGF-β from epithelial cells, which was not affected by cell-contact. In contrast, the extracellular microvesicles, exosomes derived from cocultured cells partly contributed to cell-to-cell contact-mediated viral transmission. Taken together, our findings support a role for TGF-β derived from epithelial cells in efficient viral transmission, which fosters induction of the viral lytic cycle in the donor B cells.
Rights: http://creativecommons.org/licenses/by/4.0/
Type: article
URI: http://hdl.handle.net/2115/70996
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 南保 明日香

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