Source:http://linkedlifedata.com/resource/pubmed/id/17484137
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:dateCreated |
2007-5-8
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| pubmed:abstractText |
Human Immunodeficiency Virus type 1 (HIV-1) infection can now be treated effectively in many patients in the developed world, using combinations of antiretroviral therapeutics, called Highly Active Anti-Retroviral Therapy (HAART). However, despite prolonged treatment with HAART, the persistence of latently HIV-1-infected cellular reservoirs harboring transcriptionally silent but replication-competent proviruses represents the major hurdle to virus eradication. These latently infected cells are a permanent source for virus reactivation and lead to a rebound of the viral load after interruption of HAART. Therefore, a greater understanding of the molecular mechanisms regulating proviral latency and reactivation should lead to rational strategies aimed at purging these cellular reservoirs of HIV-1. This review summarizes our current knowledge and understanding of the elements involved in HIV-1 transcriptional reactivation: (1) the site of integration; (2) the transcription factor NF-kappaB, which is induced by proinflammatory cytokines (such as TNFalpha) and binds to two kappaB sites in the HIV-1 promoter region; (3) the specific remodeling of a single nucleosome (called nuc-1 and located immediately downstream of the HIV-1 transcription start site under latency conditions) upon activation of the HIV-1 promoter; (4) post-translational acetylation of histones and of non-histone proteins (following treatment with deacetylases inhibitors, which induce viral transcription and nuc-1 remodeling); and (5) the viral trans-activator Tat, which promotes transcription by mediating the recruitment to the HIV-1 promoter of histone-modifying enzymes and ATP-dependent chromatin remodeling complexes required for nucleosome disruption and transcriptional processivity. Finally, this review highlights experimental therapies aimed at administrating HIV-1 gene expression activators (such as HDAC inhibitors) combined with an effective HAART in order to reactivate and decrease/eliminate the pool of latently HIV-1-infected cellular reservoirs
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-HIV Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyribonuclease I,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Gene Products, tat,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Acetyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases,
http://linkedlifedata.com/resource/pubmed/chemical/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/Nucleosomes,
http://linkedlifedata.com/resource/pubmed/chemical/tat Gene Products, Human...
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| pubmed:status |
MEDLINE
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| pubmed:issn |
0306-0225
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
41
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
371-96
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:17484137-Acetylation,
pubmed-meshheading:17484137-Adenosine Triphosphate,
pubmed-meshheading:17484137-Animals,
pubmed-meshheading:17484137-Anti-HIV Agents,
pubmed-meshheading:17484137-Chromatin,
pubmed-meshheading:17484137-Chromatin Assembly and Disassembly,
pubmed-meshheading:17484137-Deoxyribonuclease I,
pubmed-meshheading:17484137-Enzyme Inhibitors,
pubmed-meshheading:17484137-Gene Products, tat,
pubmed-meshheading:17484137-HIV Long Terminal Repeat,
pubmed-meshheading:17484137-HIV-1,
pubmed-meshheading:17484137-Histone Acetyltransferases,
pubmed-meshheading:17484137-Histone Deacetylase Inhibitors,
pubmed-meshheading:17484137-Histone Deacetylases,
pubmed-meshheading:17484137-Histones,
pubmed-meshheading:17484137-Humans,
pubmed-meshheading:17484137-Nucleosomes,
pubmed-meshheading:17484137-Protein Processing, Post-Translational,
pubmed-meshheading:17484137-Transcription, Genetic,
pubmed-meshheading:17484137-Virus Integration,
pubmed-meshheading:17484137-Virus Latency,
pubmed-meshheading:17484137-tat Gene Products, Human Immunodeficiency Virus
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| pubmed:year |
2007
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| pubmed:articleTitle |
Chromatin-associated regulation of HIV-1 transcription: implications for the development of therapeutic strategies.
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| pubmed:affiliation |
University Libre de Bruxelles, Institut de Biologie et de Médecine Moléculaíres, Laboratoire de Virologie Moléculaire, 12, rue des Professeurs Jeener et Brachet 6041 Gosselies, Belgium.
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| pubmed:publicationType |
Journal Article,
Review,
Research Support, Non-U.S. Gov't
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