TRAF activation of C/EBPbeta (NF-IL6) via p38 MAPK induces HIV-1 gene expression in monocytes/macrophages.

Abstract:

:C/EBPbeta plays a pivotal role in activation of human immunodeficiency virus type 1 (HIV-1) in monocytes/macrophages. However, mechanisms for functional regulation of C/EBPbeta remain uncharacterized. Previous studies indicated that NF-kappaB 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-kappaB 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-kappaB, 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/EBPbeta, and that activation of p38 MAPK potently activates C/EBPbeta-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 TRAF-p38 MAPK-CEBPbeta pathway provides a new target for controlling reactivation of latent HIV-1 in monocytes/macrophages.

journal_name

Microbes Infect

journal_title

Microbes and infection

authors

Horie R,Ishida T,Maruyama-Nagai M,Ito K,Watanabe M,Yoneyama A,Higashihara M,Kimura S,Watanabe T

doi

10.1016/j.micinf.2007.02.017

subject

Has Abstract

pub_date

2007-05-01 00:00:00

pages

721-8

issue

6

eissn

1286-4579

issn

1769-714X

pii

S1286-4579(07)00095-0

journal_volume

9

pub_type

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