Journal
MICROBES AND INFECTION
Volume 9, Issue 6, Pages 721-728Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.micinf.2007.02.017
Keywords
TRAF; p38 MAPK; C/EBP beta (NF-IL6); HIV-1
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C/EBP beta plays a pivotal role in activation of human immunodeficiency virus type 1 (HIV-1) in monocytes/macrophages. However, mechanisms for functional regulation of C/EBP beta remain uncharacterized. Previous studies indicated that NF-kappa B activation by tumor necrosis factor (TNF) receptor family, which activates TNF receptor associated factor (TRAF), induces HIV-1 expression. We found that TRAF signals activate HIV-1 LTR with mutations of NF-kappa B sites in promonocytic cell line U937, suggesting existence of an alternative HIV-1 activating pathway. In this study, we have characterized the signal transduction pathway of TRAF other than that leading to NF-kappa B, using U937 cell line, and its subline, U1, which is chronically infected by HIV-1. We show that signals downstream of TRAF2 and TRAF5 activate p38 MAPK, which directly phosphorylates C/EBP beta and that activation of p38 MAPK potently activates C/EBP beta-mediated induction of HIV-1 gene expression. We also show TRAF2 and TRAF5 are expressed in monocytes/macrophages of spleen samples from HIV-1 infected patients. Identification of TRAFp38 MAPK-CEBP beta pathway provides a new target for controlling reactivation of latent HIV-1 in monocytes/macrophages. (C) 2007 Elsevier Masson SAS. All rights reserved.
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