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rdf:type |
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lifeskim:mentions |
umls-concept:C0019682,
umls-concept:C0042774,
umls-concept:C0063690,
umls-concept:C0767950,
umls-concept:C1167622,
umls-concept:C1335268,
umls-concept:C1514559,
umls-concept:C1514562,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221
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pubmed:issue |
23
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pubmed:dateCreated |
2006-11-13
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pubmed:abstractText |
We initially identified lens epithelium-derived growth factor/p75 (LEDGF/p75) as a binding partner of human immunodeficiency virus type 1 (HIV-1) integrase. To investigate the role of LEDGF/p75 in HIV replication and its potential as a new antiviral target, we stably overexpressed two different fragments containing the integrase binding domain (IBD) of LEDGF/p75 fused to enhanced green fluorescent protein (eGFP). HIV-1 replication was severely inhibited by overexpression of the eGFP-IBD fusion proteins, while no inhibition was observed in cell lines overexpressing the interaction-deficient D366A mutant. Quantitative PCR pinpointed the block to the integration step, whereas nuclear import was not affected. Competition of the IBD fusion proteins with endogenous LEDGF/p75 for binding to integrase led to a potent defect in HIV-1 replication in both HeLaP4- and MT-4-derived cell lines. A previously described diketo acid-resistant HIV-1 strain remained fully susceptible to inhibition, suggesting that this strategy will also work in patients who harbor strains resistant to the current experimental integrase inhibitors. These data support LEDGF/p75 as an important cofactor for HIV replication and provide proof of concept for the LEDGF/p75-integrase interaction as a novel target for treating HIV-1 infection.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-10219094,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-10233971,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-10366569,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-10623627,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-10649997,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-10877832,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-11027629,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-11035935,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-11479624,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-11975850,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-12368302,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-12407101,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-12637625,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-12663775,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-12796494,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-13130095,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-14557631,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-14973078,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-14998998,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-15163664,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-15308744,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-15353349,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-15371438,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-15707975,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-15749713,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-15797927,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-15851015,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-15855167,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-15895093,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-16260736,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-16311605,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-16318853,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-16403635,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-16439544,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-16735438,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-6200935,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-7801128,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-8202502,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-9306402,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-9512562,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987986-9822615
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0022-538X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
80
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
11498-509
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:16987986-Cell Line,
pubmed-meshheading:16987986-Gene Expression,
pubmed-meshheading:16987986-HIV-1,
pubmed-meshheading:16987986-Humans,
pubmed-meshheading:16987986-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:16987986-Lens, Crystalline,
pubmed-meshheading:16987986-Transduction, Genetic,
pubmed-meshheading:16987986-Virus Integration,
pubmed-meshheading:16987986-Virus Replication
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pubmed:year |
2006
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pubmed:articleTitle |
Overexpression of the lens epithelium-derived growth factor/p75 integrase binding domain inhibits human immunodeficiency virus replication.
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pubmed:affiliation |
Molecular Medicine, KU Leuven and IRC KULAK, Kapucijnenvoer 33 VCTB+5, B-3000 Leuven, Belgium.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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