title: Metabolic activation of nucleoside and nucleotide reverse transcriptase inhibitors in dendritic and Langerhans cells.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Virology & Chemotherapy, Rega Institute for Medical Research, B-3000 Leuven, Belgium. jan.balzarini@rega.kuleuven.ac.be
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Yven
authors.initials: Y
authors.lastname: Van Herrewege
authors.forename: Guido
authors.initials: G
authors.lastname: Vanham
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000378:metabolism*; D019380:Anti-HIV Agents / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000378:metabolism*; D007801:Langerhans Cells / Q000378:metabolism / Q000821:virology*; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000378:metabolism*; D010641:Phenotype; D018894:Reverse Transcriptase Inhibitors / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology; D000068698:Tenofovir; D015215:Zidovudine / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D000068698:Tenofovir; D000225:Adenine