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 K-i values and the K-i/K-m ratios for mutated, recombinant M184V human immunodeficiency virus type 1 revers e transcriptase (RT) for (-)2'-dideoxy-3'-thiacytidine triphosphate (3 TCTP) 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 assa ys showed that viruses containing the M184V substitution were highly r esistant to 3TCTP, with an increase in the 50% inhibitory concentratio n of 250-fold in comparison with wild-type recombinant virus.