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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5310
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pubmed:dateCreated |
1997-4-28
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pubmed:abstractText |
The chemokine receptors CXCR4 and CCR5 have recently been shown to act as coreceptors, in concert with CD4, for human immunodeficiency virus-type 1 (HIV-1) infection. RANTES and other chemokines that interact with CCR5 and block infection of peripheral blood mononuclear cell cultures inhibit infection of primary macrophages inefficiently at best. If used to treat HIV-1-infected individuals, these chemokines could fail to influence HIV replication in nonlymphocyte compartments while promoting unwanted inflammatory side effects. A derivative of RANTES that was created by chemical modification of the amino terminus, aminooxypentane (AOP)-RANTES, did not induce chemotaxis and was a subnanomolar antagonist of CCR5 function in monocytes. It potently inhibited infection of diverse cell types (including macrophages and lymphocytes) by nonsyncytium-inducing, macrophage-tropic HIV-1 strains. Thus, activation of cells by chemokines is not a prerequisite for the inhibition of viral uptake and replication. Chemokine receptor antagonists like AOP-RANTES that achieve full receptor occupancy at nanomolar concentrations are strong candidates for the therapy of HIV-1-infected individuals.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD4,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL4,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL5,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Inflammatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CCR5,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Chemokine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytokine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, HIV
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0036-8075
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
276-9
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pubmed:dateRevised |
2007-11-19
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pubmed:meshHeading |
pubmed-meshheading:9092481-Animals,
pubmed-meshheading:9092481-Antigens, CD4,
pubmed-meshheading:9092481-Binding, Competitive,
pubmed-meshheading:9092481-Cats,
pubmed-meshheading:9092481-Cell Line,
pubmed-meshheading:9092481-Cells, Cultured,
pubmed-meshheading:9092481-Chemokine CCL4,
pubmed-meshheading:9092481-Chemokine CCL5,
pubmed-meshheading:9092481-Chemotaxis, Leukocyte,
pubmed-meshheading:9092481-HIV-1,
pubmed-meshheading:9092481-HeLa Cells,
pubmed-meshheading:9092481-Humans,
pubmed-meshheading:9092481-Macrophage Inflammatory Proteins,
pubmed-meshheading:9092481-Macrophages,
pubmed-meshheading:9092481-Receptors, CCR5,
pubmed-meshheading:9092481-Receptors, Chemokine,
pubmed-meshheading:9092481-Receptors, Cytokine,
pubmed-meshheading:9092481-Receptors, HIV,
pubmed-meshheading:9092481-T-Lymphocytes,
pubmed-meshheading:9092481-Virus Replication
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pubmed:year |
1997
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pubmed:articleTitle |
Potent inhibition of HIV-1 infectivity in macrophages and lymphocytes by a novel CCR5 antagonist.
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pubmed:affiliation |
Virology Group, Chester Beatty Laboratories, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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