This Article Full Text (PDF) Other Versions of this Article: JVI.00752-08v1 82/21/10436    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Lu, F. Articles by Lieberman, P. M. PubMed PubMed Citation Articles by Lu, F. Articles by Lieberman, P. M.

 Previous Article  |  Next Article 

J. Virol. doi:10.1128/JVI.00752-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

EBV Induced miR-155 Attenuates NF-B Signaling And Stabilizes Latent Virus Persistence

The Wistar Institute, Philadelphia, PA 19104; Comprehensive Cancer Center, Ohio State University, Columbus Ohio 43210

^* To whom correspondence should be addressed. Email: Lieberman{at}wistar.upenn.edu.

	Abstract

MicroRNAs have been implicated in the modulation of gene expression programs important for normal and cancer cell development. MiR-155 is known to play a role in B-cell development and is upregulated in various B-cell lymphomas, including several that are latently infected with Epstein-Barr Virus (EBV). We show here that EBV infection of primary human B-lymphocytes leads to the sustained elevation of miR-155 and its precursor RNA, BIC. The EBV encoded latency membrane protein 1 (LMP1) can partially reconstitute BIC activation in B-lymphocytes, but not in epithelial cell cultures. LMP1 is a potent activator of NF-B signaling pathways and is essential for EBV immortalization of B-lymphocytes. An inhibitor to miR-155 further stimulated NF-B responsive gene transcription, and IKK was identified as a potential target of miR-155 translational repression. Remarkably, miR-155 inhibitor reduced EBNA1 mRNA and EBV copy number in latently infected cells. This suggests that miR-155 contributes to EBV immortalization by modulation of NF-B signaling and the suppression of host-innate immunity to latent viral infection.