open access

https://hdl.handle.net/2115/52109

Roles of Cell Signaling Pathways in Cell-to-Cell Contact-Mediated Epstein-Barr Virus Transmission

英語

2012-09

American Society for Microbiology

Journal of Virology

86(17)

9285-9296

Epstein-Barr virus (EBV), a human gamma herpesvirus, establishes a life-long latent infection in B lymphocytes and epithelial cells following primary infection. Several lines of evidence indicate that the efficiency of EBV infection in epithelial cells is accelerated up to 10^[4]-fold by co-culturing with EBV-infected Burkitt's lymphoma (BL) cells compared with infection with cell-free virions, indicating that EBV infection into epithelial cells is mainly mediated via cell-to-cell contact. However, the molecular mechanisms involved in this pathway are poorly understood. Here, we establish a novel assay to assess cell-to-cell contact-mediated EBV transmission by co-culturing an EBV-infected BL cell line with an EBV-negative epithelial cell line under the stimulation for lytic cycle induction. By using this assay we confirmed that EBV was transmitted from BL cells to epithelial cells via cell-to-cell contact but not via cell-to-cell fusion. The inhibitor treatments of extracellular signal-regulated kinase (ERK) and nuclear factor (NF)-κB pathways blocked EBV transmission in addition to lytic induction. The blockage of phosphoinositide 3-kinase (PI3K) pathway impaired EBV transmission coupled with inhibition of the lytic induction. Knockdown of the RelA/p65 subunit of NF-κB reduced viral transmission. Moreover these signaling pathways were activated in co-cultured BL cells and in epithelial cells. Finally we observed that the viral replication was induced in co-cultured BL cells. Taken together, our data suggest that cell-to-cell contact induces multiple cell signaling pathways in BL cells and epithelial cells, contributing to the induction of the viral lytic cycle in BL cells and the enhancement of viral transmission to epithelial cells.

学術雑誌論文

Accepted Manuscript

© 2012 American Society for Microbiology

0022-538X