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Epstein-Barr Virus LMP2A Imposes Sensitivity to Apoptosis

Overview
Journal J Gen Virol
Specialty Microbiology
Date 2010 May 21
PMID 20484564
Citations 15
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Abstract

In cell lines, the Epstein-Barr virus (EBV)-encoded protein latent membrane protein 2A (LMP2A) protects B-cells from apoptosis by blocking B-cell receptor (BCR) signalling. However, EBV-infected B-cells in vivo are extremely different from cell lines. This study used a murine transgenic model in which B-cells express LMP2A and a BCR specific for hen egg lysozyme to determine whether LMP2A protects resting and antigen-activated B-cells from apoptosis. LMP2A allows BCR signal transduction and induces constitutive activation of NF-kappaB to increase Bcl-2 levels that afford LMP2A-mediated protection from apoptosis in the absence or presence of antigen. In contrast, low levels of NF-kappaB inhibitor only affected Bcl-2 and Bcl-xL levels and increased apoptosis in LMP2A-negative B-cells after BCR cross-linking. These data suggest that LMP2A uniquely makes resting B-cells sensitive to NF-kappaB inhibition and apoptosis and suggest that NF-kappaB may be a novel target to eradicate latently EBV-infected B-cells.

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References
1.
CALDWELL R, Wilson J, Anderson S, Longnecker R . Epstein-Barr virus LMP2A drives B cell development and survival in the absence of normal B cell receptor signals. Immunity. 1998; 9(3):405-11. DOI: 10.1016/s1074-7613(00)80623-8. View

2.
Portis T, Longnecker R . Epstein-Barr virus (EBV) LMP2A mediates B-lymphocyte survival through constitutive activation of the Ras/PI3K/Akt pathway. Oncogene. 2004; 23(53):8619-28. DOI: 10.1038/sj.onc.1207905. View

3.
Kis L, Salamon D, Persson E, Nagy N, Scheeren F, Spits H . IL-21 imposes a type II EBV gene expression on type III and type I B cells by the repression of C- and activation of LMP-1-promoter. Proc Natl Acad Sci U S A. 2010; 107(2):872-7. PMC: 2818931. DOI: 10.1073/pnas.0912920107. View

4.
Lung R, Tong J, Sung Y, Leung P, Ng D, Chau S . Modulation of LMP2A expression by a newly identified Epstein-Barr virus-encoded microRNA miR-BART22. Neoplasia. 2009; 11(11):1174-84. PMC: 2767219. DOI: 10.1593/neo.09888. View

5.
Babcock G, Thorley-Lawson D . Tonsillar memory B cells, latently infected with Epstein-Barr virus, express the restricted pattern of latent genes previously found only in Epstein-Barr virus-associated tumors. Proc Natl Acad Sci U S A. 2000; 97(22):12250-5. PMC: 17327. DOI: 10.1073/pnas.200366597. View