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Metabolic activation of nucleoside and nucleotide reverse transcriptase inhibitors in dendritic and Langerhans cells

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Show simple item record Balzarini, J. en_US Van Herrewege, Y. en_US Vanham, G. en_US 2007-12-06T14:46:26Z 2007-12-06T14:46:26Z 2002 en_US
dc.identifier.issn 0269-9370 en_US
dc.identifier.other ITG-M2A en_US
dc.identifier.other ITG-MLA en_US
dc.identifier.other MICRO en_US
dc.identifier.other U-IMMUN en_US
dc.identifier.other JIF en_US
dc.identifier.other ABSTRACT en_US
dc.description Not the final published version
dc.description.abstract BACKGROUND: Langerhans cells and interstitial dendritic cells are the earliest targets for HIV infection through sexual transmission of HIV. Metabolism of nucleoside analogues markedly differs in proliferating T lymphocytes and resting monocyte/macrophages, and thus their antiviral efficacy can substantially differ between both cell types. METHODS: The metabolism of radio-labelled zidovudine (ZDV), lamivudine (3TC) and tenofovir (PMPA) to their antivirally active metabolites was studied in primary cells, representative of early in vivo targets of HIV [i.e. monocyte-derived dendritic cells (MO-DC), MO-derived Langerhans cells (MO-LC), PHA/IL-2-activated T-blast cells] as well as in a laboratory T-lymphocyte (CEM) cell line. RESULTS: Whereas lamivudine metabolism to its active triphosphate derivative (3TC-TP) did not markedly differ between T-cells and MO-derived LC and DC, zidovudine was much better converted to ZDV-TP in T-cells than in MO-LC and MO-DC. In contrast, tenofovir was markedly more abundantly converted to its antivirally active diphosphate metabolite PMPApp in MO-DC and MO-LC than zidovudine and lamivudine. CONCLUSION: Our metabolic data suggest that tenofovir may be superior to zidovudine and lamivudine for inhibition of HIV replication in dendritic/Langerhans cells, the first-line cell types targeted by a primary HIV infection. en_US
dc.language English en_US
dc.publisher Lippincott, Williams & Wilkins
dc.subject Viral diseases en_US
dc.subject HIV en_US
dc.subject AIDS en_US
dc.subject Antiretrovirals en_US
dc.subject Post-exposure en_US
dc.subject Zidovudine en_US
dc.subject Lamivudine en_US
dc.subject Tenofovir en_US
dc.subject Efficacy en_US
dc.subject Virus replication en_US
dc.subject Monocytes en_US
dc.subject Dendritic cells en_US
dc.subject Langerhans cells en_US
dc.subject T lymphocytes en_US
dc.title Metabolic activation of nucleoside and nucleotide reverse transcriptase inhibitors in dendritic and Langerhans cells en_US
dc.type Article en_US
dc.citation.jtitle AIDS en_US
dc.citation.volume 16 en_US
dc.citation.pages 2159-2163 en_US Philadelphia
dc.citation.jabbreviation AIDS en_US

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