Endogenous reverse transcription assays reveal high-level resistance to the triphosphate of (-)2'-dideoxy-3'-thiacytidine by mutated M184V human immunodeficiency virus type 1.
Kinetic analysis showed that the Ki values and the Ki/Km ratios for mutated, recombinant M184V human immunodeficiency virus type 1 reverse transcriptase (RT) for (-)2'-dideoxy-3'-thiacytidine triphosphate (3TCTP) were 35-fold higher than the equivalent values for wild-type RT but only about twice as high as the equivalent values for each of the triphosphates of ddC (ddCTP) and ddA (ddATP). Fully endogenous RT assays showed that viruses containing the M184V substitution were highly resistant to 3TCTP, with an increase in the 50% inhibitory concentration of 250-fold in comparison with wild-type recombinant virus.
Quan
Y
Y
McGill University AIDS Centre, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.
Gu
Z
Z
Li
X
X
Li
Z
Z
Morrow
C D
CD
Wainberg
M A
MA
D019380:Anti-HIV Agents / Q000494:pharmacology*; D003838:Deoxyadenine Nucleotides / Q000378:metabolism / Q000494:pharmacology*; D054306:Dideoxynucleotides; D004351:Drug Resistance; D054303:HIV Reverse Transcriptase / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000378:metabolism / Q000494:pharmacology*; D009154:Mutation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D019380:Anti-HIV Agents; D003838:Deoxyadenine Nucleotides; D054306:Dideoxynucleotides; D011994:Recombinant Proteins; C037773:2',3'-dideoxyadenosine triphosphate; D019259:Lamivudine; D054303:HIV Reverse Transcriptase