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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1998-3-12
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pubmed:databankReference | |
pubmed:abstractText |
Unlike the selection of HIV-1 variants resistant to anti-retroviral drugs in human peripheral blood mononuclear cells and T cell lines, induction of resistance in monocyte-derived macrophages has not been widely studied. Since macrophages serve as a potential HIV-1 reservoir in humans, knowledge of the effect of anti-retroviral drugs on macrophage-tropic HIV-1 isolates may help in the design of a strategy for prolonged suppression of viral replication. In-vitro selection and drug susceptibility testing of macrophage-tropic HIV-1 variants with reduced sensitivity to two non-nucleoside reverse transcriptase inhibitors, atevirdine and delavirdine (both bis-heteroarylpiperazines), is described here. The atevirdine-resistant isolate was cross-resistant to delavirdine, and the delavirdine-resistant isolate was cross-resistant to atevirdine. Interestingly, the atevirdine-resistant isolate, but not the delavirdine-resistant isolate, was also cross-resistant to nevirapin while the inhibition of viral replication of both isolates in macrophages by zidovudine was the same as that in the parental HIV-1 strain. Nucleotide sequence analysis of the resistant macrophage-tropic HIV-1 isolates showed that the atevirdine-induced resistance was due to a single amino acid change at codon 106 and that the delavirdine-induced resistance could be attributed to an amino acid change at codon 236. This study demonstrates that monocyte-derived macrophages can be used to investigate the phenotypic and genotypic acquisition of anti-retroviral drug resistance of macrophage-tropic HIV-1.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Delavirdine,
http://linkedlifedata.com/resource/pubmed/chemical/HIV Reverse Transcriptase,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Reverse Transcriptase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Zidovudine,
http://linkedlifedata.com/resource/pubmed/chemical/atevirdine
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0305-7453
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
40
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
847-53
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:9462437-Amino Acid Sequence,
pubmed-meshheading:9462437-Delavirdine,
pubmed-meshheading:9462437-Drug Resistance, Microbial,
pubmed-meshheading:9462437-HIV Reverse Transcriptase,
pubmed-meshheading:9462437-HIV-1,
pubmed-meshheading:9462437-Humans,
pubmed-meshheading:9462437-Macrophages,
pubmed-meshheading:9462437-Molecular Sequence Data,
pubmed-meshheading:9462437-Monocytes,
pubmed-meshheading:9462437-Piperazines,
pubmed-meshheading:9462437-Reverse Transcriptase Inhibitors,
pubmed-meshheading:9462437-Sequence Homology, Amino Acid,
pubmed-meshheading:9462437-Zidovudine
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pubmed:year |
1997
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pubmed:articleTitle |
In-vitro selection of HIV-1 variants resistant to non-nucleoside reverse transcriptase inhibitors in monocyte-derived macrophages.
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pubmed:affiliation |
Eijkman-Winkler Institute of Medical Microbiology, University of Utrecht, University Hospital, The Netherlands.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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