Synergistic activation of human immunodeficiency virus type 1 promoter activity by NF-kappa B and inhibitors of deacetylases: Potential perspectives for the development of therapeutic strategies
[en] The transcription factor NF-kappaB plays a central role in the human immunodeficiency virus type 1 (HIV-1) activation pathway. HIV-1 transcription is also regulated by protein acetylation, since treatment with deacetylase inhibitors such as trichostatin A (TSA) or sodium butyrate (NaBut) markedly induces HIV-1 transcriptional activity of the long terminal repeat (LTR) promoter. Here, we demonstrate that TSA (NaBut) synergized with both ectopically expressed p50/p65 and tumor necrosis factor alpha/SF2 (TNF)-induced NF-kappaB to activate the LTR. This was confirmed for LTRs from subtypes A through G of the HIV-1 major group, with a positive correlation between the number Of kappaB sites present in the LTRs and the amplitude of the TNF-TSA synergism. Mechanistically, TSA (NaBut) delayed the cytoplasmic recovery of the inhibitory protein IkappaBalpha. This coincided with a prolonged intranuclear presence and DNA binding activity of NF-kappaB. The physiological relevance of the TNF-TSA (NaBut) synergism was shown on HIV-1 replication in both acutely and latently HIV-infected cell lines. Therefore, our results open new therapeutic strategies aimed at decreasing or eliminating the pool of latently HIV-infected reservoirs by forcing viral expression.
Research Center/Unit :
Giga-Signal Transduction - ULiège
Disciplines :
Immunology & infectious disease
Author, co-author :
Quivy, Vincent
Adam, Emmanuelle
Collette, Yves
Demonte, Dominique
Chariot, Alain ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Synergistic activation of human immunodeficiency virus type 1 promoter activity by NF-kappa B and inhibitors of deacetylases: Potential perspectives for the development of therapeutic strategies
Publication date :
November 2002
Journal title :
Journal of Virology
ISSN :
0022-538X
eISSN :
1098-5514
Publisher :
Amer Soc Microbiology, Washington, United States - Washington
Volume :
76
Issue :
21
Pages :
11091-11103
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique Télévie FBC ULg. ARC - Université de Liège. Actions de Recherche Concertées
Funding text :
This work was supported by grants to C.V.L. from the Fonds National de la Recherche Scientifique (FNRS, Belgium), the Telévie-Program, the Université Libre de Bruxelles (ULB), the Internationale Brachet Stiftung, the CGRI-INSERM cooperation, the Région Wallonne-Commission Européenne FEDER, the Agence Nationale de Recherches sur le SIDA (ANRS, France), and the Theyskens-Mineur Foundation. V.Q. is an Aspirant of the FNRS. A.C. is a Chercheur Qualifié of the FNRS. J.P. and V.B. are Directeurs de Recherches of the FNRS. C.V.L. is a Maître de Recherches of the FNRS. E.A. and
D.D. are supported by postdoctoral fellowships from the ULB (ARC
program 98/03-224) and the Re´gion Wallonne (grant 991/4202), respectively. R.C. is supported by a fellowship from the Agence Nationale
de Recherches sur le SIDA (France).
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