title: Epstein-Barr virus-induced miR-155 attenuates NF-kappaB signaling and stabilizes latent virus persistence.
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-kappaB signaling pathways and is essential for EBV immortalization of B lymphocytes. An inhibitor to miR-155 further stimulated NF-kappaB responsive gene transcription, and IKKepsilon was identified as a potential target of miR-155 translational repression. Remarkably, miR-155 inhibitor reduced EBNA1 mRNA and the EBV copy number in latently infected cells. This suggests that miR-155 contributes to EBV immortalization by modulation of NF-kappaB signaling and the suppression of host innate immunity to latent viral infection.
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Lu
authors.forename: Andreas
authors.initials: A
authors.lastname: Weidmer
authors.forename: Chang-Gong
authors.initials: CG
authors.lastname: Liu
authors.forename: Stefano
authors.initials: S
authors.lastname: Volinia
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
authors.forename: Paul M
authors.initials: PM
authors.lastname: Lieberman