Original Article
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Virology. Nov 12, 2014; 3(4): 22-29
Published online Nov 12, 2014. doi: 10.5501/wjv.v3.i4.22
Nuclear factor κB represses the expression of latent membrane protein 1 in Epstein-Barr virus transformed cells
Mingxia Cao, Qianli Wang, Amy Lingel, Luwen Zhang
Mingxia Cao, Qianli Wang, Amy Lingel, Luwen Zhang, School of Biological Sciences, University of Nebraska, Lincoln, NE 68588, United States
Luwen Zhang, 238 Morrison Center, School of Biological Sciences, Nebraska Center for Virology, University of Nebraska, Lincoln, NE 68583-0900, United States
Author contributions: All authors contributed to this paper.
Supported by Grants from the NIH CA138213, RR15635, and Department of Defense W81XWH-12-1-0225 (Luwen Zhang); Qianli Wang was partially supported by Undergraduate Creative Activities and Research Experiences and Beckman Scholars Program
Correspondence to: Luwen Zhang, PhD, 238 Morrison Center, School of Biological Sciences, Nebraska Center for Virology, University of Nebraska, 4240 Fair St., Lincoln, NE 68583-0900, United States. lzhang2@unl.edu
Telephone: +1-402-4725905 Fax: +1-402-4723323
Received: April 15, 2014
Revised: July 14, 2014
Accepted: September 18, 2014
Published online: November 12, 2014
Processing time: 212 Days and 12.6 Hours
Abstract

AIM: To investigate the role of nuclear factor κB (NF-κB) in the regulation of Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) in EBV transformed cells.

METHODS: LMP1 expression was examined in EBV transformed human B lymphocytes with modulation of NF-κB activity.

RESULTS: EBV infection is associated with several human cancers. EBV LMP1 is required for efficient transformation of adult primary B cells in vitro, and is expressed in several pathogenic stages of EBV-associated cancers. Regulation of EBV LMP1 involves both viral and cellular factors. LMP1 activates NF-κB signaling pathway that is a part of the EBV transformation program. However, the relation between NF-κB and LMP1 expression is not well established yet. In this report, we found that blocking the NF-κB activity by Inhibitor of κB stimulated LMP1 expression, while the overexpression of NF-κB repressed LMP1 expression in EBV-transformed IB4 cells. In addition, LMP1 repressed its own promoter activities in reporter assays, and the repression was associated with the activation of NF-κB. Moreover, NF-κB alone is sufficient to repress LMP1 promoter activities.

CONCLUSION: Our data suggest LMP1 may repress its own expression through NF-κB in EBV transformed cells and shed a light on LMP1 regulation during EBV transformation.

Keywords: Nuclear factor κB; Epstein-Barr virus; Latent membrane protein 1; Latency; Transformation

Core tip: We find a classical feedback inhibition of Epstein Barr virus (EBV) Latent membrane protein 1 (LMP1) and nuclear factor κB (NF-κB): LMP1 activates NF-κB, and NF-κB inhibits LMP1 expression. The regulatory loop may benefit EBV transformation processes.