Epstein-Barr virus represses Fox01 transcription factor through Latent Membrane Protein 1 and Latent Membrane Protein 2A

AM Shore, PC White, RC Hui, A Essafi, EW Lam, Martin Rowe, P Brennan

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Epstein-Barr virus (EBV) infection is associated with the development of many B-cell lymphomas, including Burkitt's lymphoma, Hodgkin's lymphoma, and posttransplant lymphoproliferative disease. The virus alters a diverse range of cellular molecules, which leads to B-cell growth and immortalization. This study was initiated to investigate the interplay between EBV and a proapoptotic transcription factor target, FoxO1. In this report, we show that EBV infection of B cells leads to the downregulation of FoxO1 expression by phosphatidylinositol 3-kinase-mediated nuclear export, by inhibition of FoxO1 mRNA expression, and by alteration of posttranslational modifications. This repression directly correlates with the expression of the FoxO1 target gene Bcl-6 and inversely correlates with the FoxO1-regulated gene Cyclin D2. Expression of the EBV genes for latent membrane protein 1 and latent membrane protein 2A decreases FoxO1 expression. Thus, our data elucidate distinct mechanisms for the regulation of the proapoptotic transcription factor FoxO1 by EBV.
Original languageEnglish
Pages (from-to)11191-11199
Number of pages9
JournalJournal of virology
Volume80
DOIs
Publication statusPublished - 13 Sep 2006

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