rdf:type |
|
lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0035253,
umls-concept:C0039194,
umls-concept:C0079532,
umls-concept:C0079904,
umls-concept:C0185117,
umls-concept:C0205112,
umls-concept:C0851285,
umls-concept:C0851827,
umls-concept:C1701901,
umls-concept:C2003941,
umls-concept:C2911684
|
pubmed:dateCreated |
2007-9-21
|
pubmed:abstractText |
BACKGROUND: In HIV-infected T lymphocytes, NF-kappaB/Rel transcription factors are major elements involved in the activation of LTR-dependent transcription from latency. Most NF-kappaB heterodimer p65/p50 is sequestered as an inactive form in the cytoplasm of resting T lymphocytes via its interaction with I kappaB inhibitors. In these cells, both absolute HIV latency and low level ongoing HIV replication have been described. These situations could be related to differences in the balance between NF-kappaB and I kappaB alpha ratio. Actually, control of I kappaB alpha by cellular factors such as Murr-1 plays a critical role in maintaining HIV latency in unstimulated T lymphocytes. Formerly, our group demonstrated the presence of nuclear I kappaB alpha in T cells after PMA activation. Now we attempt to determine the dynamics of NF-kappaB/I kappaB alpha nucleocytosolic transport in absence of activation as a mechanism to explain both the maintenance of latency and the existence of low level ongoing HIV replication in resting CD4+ T lymphocytes. RESULTS AND CONCLUSION: We show that the inhibition of the nuclear export by leptomycin B in resting CD4+ T cells resulted in nuclear accumulation of both I kappaB alpha and p65/RelA, as well as formation of NF-kappaB/I kappaB alpha complexes. This proves the existence of a rapid shuttling of I kappaB alpha between nucleus and cytosol even in absence of cellular activation. The nuclear accumulation of I kappaB alpha in resting CD4+ T lymphocytes results in inhibition of HIV-LTR dependent transcription as well as restrains HIV replication in CD4+ T lymphocytes. On the other hand, basal NF-kappaB activity detected in resting CD4+ T lymphocytes was related to low level HIV replication in these cells.
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-10037782,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-10102628,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-10341281,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-10364191,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-10558989,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-10581242,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-10655476,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-10747893,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-10837072,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-11024020,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-11160127,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-11672548,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-11801607,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-12360211,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-12525599,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-12594269,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-12960235,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-14593121,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-14685242,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-15064398,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-15220005,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-15308706,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-15613239,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-16254353,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-2023633,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-3016298,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-3031512,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-3412474,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-7489410,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-7565415,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-7729429,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-7739525,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-7739549,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-8119981,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-8709193,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-8717528,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-9057089,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-9360926,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-9360927,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17686171-9516441
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
|
pubmed:status |
MEDLINE
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pubmed:issn |
1742-4690
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pubmed:author |
|
pubmed:issnType |
Electronic
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pubmed:volume |
4
|
pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
56
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:17686171-CD4-Positive T-Lymphocytes,
pubmed-meshheading:17686171-Cell Nucleus,
pubmed-meshheading:17686171-Cells, Cultured,
pubmed-meshheading:17686171-Cytosol,
pubmed-meshheading:17686171-DNA, Viral,
pubmed-meshheading:17686171-Gene Expression Regulation, Viral,
pubmed-meshheading:17686171-HIV Infections,
pubmed-meshheading:17686171-HIV Long Terminal Repeat,
pubmed-meshheading:17686171-HIV-1,
pubmed-meshheading:17686171-Humans,
pubmed-meshheading:17686171-I-kappa B Proteins,
pubmed-meshheading:17686171-NF-kappa B,
pubmed-meshheading:17686171-Signal Transduction,
pubmed-meshheading:17686171-Transfection,
pubmed-meshheading:17686171-Virus Replication
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pubmed:year |
2007
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pubmed:articleTitle |
Basal shuttle of NF-kappaB/I kappaB alpha in resting T lymphocytes regulates HIV-1 LTR dependent expression.
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pubmed:affiliation |
AIDS Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain. mcoiras@isciii.es
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|