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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1997-1-30
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pubmed:abstractText |
Using PCR to monitor early (LTR/LTR (long terminal repeat)) and late (LTR/gag) products of reverse transcription and the formation of HIV-1 LTR circles (indicating nuclear import), we explored the relationship between T cell activation signals and early events in the life cycle of HIV-1 infection. The combination of TCR ligation with either CD28 cross-linking or exogenous IL-2 was required for HIV-1 LTR circle formation in resting CD4+ T cells. Ligation of the TCR or CD28 receptors or addition of IL-2 alone did not induce this process. However, cross-linking the TCR, or IL-2 alone, unlike CD28 ligation, could induce the completion of viral reverse transcription. In contrast, the initiation of HIV-1 reverse transcription could occur in resting CD4+ T cells without any stimulation. Cyclosporin A (CsA), an inhibitor of T cell activation, completely blocked HIV-1 DNA nuclear import in activated CD4+ T cells. The completion of HIV-1 reverse transcription was blocked by CsA in infected CD4+ T cells activated by TCR ligation and IL-2, but not in cells stimulated by TCR and CD28 ligation. The costimulation of CD3 and CD28 mAbs in the presence of IL-2 could not overcome the CsA inhibitory effect on nuclear import of viral DNA. Therefore, the factor(s) involved in a CsA-sensitive pathway plays a critical role in HIV-1 DNA transport from the cytoplasm into the nucleus. Production and movement of HIV-1 DNA in resting CD4+ T cells require two signals: one signal from the TCR, which normally regulates the G0 to G1 transition, induces completion of viral reverse transcription; the other signal through CD28 or an IL-2R-dependent process is sensitive to CsA treatment and regulates viral DNA entry into the nucleus.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD28,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD3,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclosporine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
158
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
512-7
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8977229-Antibodies, Monoclonal,
pubmed-meshheading:8977229-Antigens, CD28,
pubmed-meshheading:8977229-Antigens, CD3,
pubmed-meshheading:8977229-Biological Transport,
pubmed-meshheading:8977229-CD4-Positive T-Lymphocytes,
pubmed-meshheading:8977229-Cell Nucleus,
pubmed-meshheading:8977229-Cyclosporine,
pubmed-meshheading:8977229-DNA, Viral,
pubmed-meshheading:8977229-HIV-1,
pubmed-meshheading:8977229-Humans,
pubmed-meshheading:8977229-Interleukin-2,
pubmed-meshheading:8977229-Interphase,
pubmed-meshheading:8977229-Lymphocyte Activation
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pubmed:year |
1997
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pubmed:articleTitle |
Nuclear import of HIV-1 DNA in resting CD4+ T cells requires a cyclosporin A-sensitive pathway.
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pubmed:affiliation |
Washington Regional Primate Research Center, University of Washington, Seattle 98195, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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