Document Detail

Roles of cell signaling pathways in cell-to-cell contact-mediated Epstein-Barr virus transmission.
MedLine Citation:
PMID:  22718812     Owner:  NLM     Status:  MEDLINE    
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 coculturing with EBV-infected Burkitt's lymphoma (BL) cells compared to 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 coculturing an EBV-infected BL cell line with an EBV-negative epithelial cell line under 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 the phosphoinositide 3-kinase (PI3K) pathway impaired EBV transmission coupled with the inhibition of lytic induction. Knockdown of the RelA/p65 subunit of NF-κB reduced viral transmission. Moreover, these signaling pathways were activated in cocultured BL cells and in epithelial cells. Finally, we observed that viral replication was induced in cocultured 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.
Asuka Nanbo; Haruna Terada; Kunihiro Kachi; Kenzo Takada; Tadashi Matsuda
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-06-20
Journal Detail:
Title:  Journal of virology     Volume:  86     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-10     Completed Date:  2012-11-05     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9285-96     Citation Subset:  IM    
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
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MeSH Terms
Cell Line
Epithelial Cells / metabolism,  virology
Epstein-Barr Virus Infections / genetics,  metabolism*,  transmission*,  virology
Extracellular Signal-Regulated MAP Kinases / genetics,  metabolism
Herpesvirus 4, Human / physiology*
Signal Transduction*
Reg. No./Substance:
EC Signal-Regulated MAP Kinases

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