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PMID: 16838299 Published · ppublish English Journal Article Review

The regulation of HIV-1 transcription: molecular targets for chemotherapeutic intervention.

Medicinal research reviews ·Vol. 26 ·No. 5 ·2006-09-00 ·Pages 595-625

Stevens M, De Clercq E, Balzarini J

Abstract

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-kappaB 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.

MeSH Terms
Animals Anti-HIV Agents/therapeutic use Drug Delivery Systems/methods Drug Design Gene Expression Regulation, Viral/drug effects,physiology HIV-1/drug effects,genetics,pathogenicity Humans Transcription, Genetic/drug effects,physiology
Chemicals
Anti-HIV Agents
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Stevens Miguel
Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
De Clercq Erik
Balzarini Jan
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Article Info
Journal
Medicinal research reviews
Abbr.
Med Res Rev
ISSN
0198-6325
DOI
10.1002/med.20081
Published
2006-09-00
Pages
595-625
Language
English
Region
United States
NLM ID
8103150
PMCID
PMC7168390
Subset
IM
External Links
PubMed source DOI: 10.1002/med.20081 PMC Full Text View journal details
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