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The regulation of HIV‐1 transcription: Molecular targets for chemotherapeutic intervention
Author(s) -
Stevens Miguel,
De Clercq Erik,
Balzarini Jan
Publication year - 2006
Publication title -
medicinal research reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.868
H-Index - 130
eISSN - 1098-1128
pISSN - 0198-6325
DOI - 10.1002/med.20081
Subject(s) - rna polymerase ii , hiv long terminal repeat , transcription (linguistics) , p tefb , biology , histone , chromatin , acetylation , microbiology and biotechnology , chromatin remodeling , histone acetyltransferases , rna , activator (genetics) , promoter , genetics , gene expression , long terminal repeat , dna , gene , linguistics , philosophy
The regulation of transcription of the human immunodeficiency virus (HIV) is a complex event that requires the cooperative action of both viral and cellular components. In latently infected resting CD4 + T cells HIV‐1 transcription seems to be repressed by deacetylation events mediated by histone deacetylases (HDACs). Upon reactivation of HIV‐1 from latency, HDACs are displaced in response to the recruitment of histone acetyltransferases (HATs) by NF‐κB or the viral transcriptional activator Tat and result in multiple acetylation events. Following chromatin remodeling of the viral promoter region, transcription is initiated and leads to the formation of the TAR element. The complex of Tat with p‐TEFb then binds the loop structures of TAR RNA thereby positioning CDK9 to phosphorylate the cellular RNA polymerase II. The Tat‐TAR‐dependent phosphorylation of RNA polymerase II plays an important role in transcriptional elongation as well as in other post‐transcriptional events. As such, targeting of Tat protein (and/or cellular cofactors) provide an interesting perspective for therapeutic intervention in the HIV replicative cycle and may afford lifetime control of the HIV infection. © 2006 Wiley Periodicals, Inc. Med Res Rev, 26, No. 5, 595–625, 2006