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: Fang Lu, Andreas Weidmer, Chang-Gong Liu, Stefano Volinia, Carlo M Croce, Paul M Lieberman
• Journal: Journal of virology (J Virol) Vol. 82 Issue 21 Pg. 10436-43 (Nov 2008) ISSN: 1098-5514 [Electronic] United States
• PMID: 18753206 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• MIRN155 microRNA, human
• MicroRNAs
• NF-kappa B

Topics

• B-Lymphocytes (virology)
• Cell Line
• Cells, Cultured
• Herpesvirus 4, Human (physiology)
• Humans
• MicroRNAs (metabolism)
• NF-kappa B (antagonists & inhibitors)
• Virus Latency