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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2002-6-21
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pubmed:abstractText |
Activation through the TCR and the costimulatory molecule CD28 influences the susceptibility of T cells to HIV-1 infection and regulates proviral gene expression. Signaling events initiated by CD28 that directly impact HIV-1 transcription have not been fully characterized. T cell lines expressing CD8alpha/28 chimeric receptors containing a mutation in tyrosine 173 to phenylalanine, which inhibits the recruitment of phosphatidylinositol 3-kinase (PI3K) to CD28, expressed higher levels of HIV-1 following T cell activation. Whereas constitutively active PI3K decreased provirus transcription, inhibiting endogenous PI3K with specific inhibitors or by overexpressing PTEN phosphatase enhanced HIV-1 expression. PI3K-dependent inhibition required the viral Tat protein and a trans activation response region element. Tat pull-down and coimmunoprecipitation experiments indicate that PI3K affects the formation of the Tat-associated kinase trans-activating complex. These studies demonstrate that PI3K negatively impacts HIV-1 transcription and that Tat activity is sensitive to T cell signaling events.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
169
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
254-60
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12077252-Animals,
pubmed-meshheading:12077252-Antigens, CD28,
pubmed-meshheading:12077252-Antiviral Agents,
pubmed-meshheading:12077252-CHO Cells,
pubmed-meshheading:12077252-Cell Line,
pubmed-meshheading:12077252-Cricetinae,
pubmed-meshheading:12077252-Down-Regulation,
pubmed-meshheading:12077252-Enzyme Activation,
pubmed-meshheading:12077252-Enzyme Inhibitors,
pubmed-meshheading:12077252-Gene Products, tat,
pubmed-meshheading:12077252-HIV-1,
pubmed-meshheading:12077252-Humans,
pubmed-meshheading:12077252-Jurkat Cells,
pubmed-meshheading:12077252-Mutagenesis, Site-Directed,
pubmed-meshheading:12077252-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:12077252-Proviruses,
pubmed-meshheading:12077252-Signal Transduction,
pubmed-meshheading:12077252-Transcription, Genetic,
pubmed-meshheading:12077252-Up-Regulation,
pubmed-meshheading:12077252-tat Gene Products, Human Immunodeficiency Virus
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pubmed:year |
2002
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pubmed:articleTitle |
Recruitment of phosphatidylinositol 3-kinase to CD28 inhibits HIV transcription by a Tat-dependent mechanism.
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pubmed:affiliation |
Graduate Program, Department of Biochemistry, Pennsylvania State University, University Park, PA 16802, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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