Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
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
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pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1742-4690
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
56
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Basal shuttle of NF-kappaB/I kappaB alpha in resting T lymphocytes regulates HIV-1 LTR dependent expression.
pubmed:affiliation
AIDS Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain. mcoiras@isciii.es
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't