INVITRO SELECTION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 RESISTANT TO 3'-AZIDO-3'-DEOXYTHYMIDINE

3'-Azido-3'-deoxythymidine (AZT)-resistant human immunodeficiency virus type 1 (HIV-1) was obtained by growing HTLV-III(B) in C8166 cell cultures in the presence of inhibitory concentrations of AZT. The AZT-resistant HIV-1 was capable of replicating, as measured by infectious virus yield, and inducing cytopathic effect in the presence of AZT concentrations able to completely suppress the replication of parental HTLV-III(B). Cloning of the AZT-resistant HIV-1 revealed that a number of different variants of HIV-1 with various degrees of sensitivity to AZT emerged during propagation of HTLV-III(B) in C8166 cells in the presence of the drug. PCR experiments performed on DNA extracted from C8166 cells infected with a resistant strain revealed that viral DNA was produced in the presence of inhibitory concentrations of AZT, while viral DNA in C8166 cells infected with the parental virus was drastically inhibited. Reverse transcriptase isolated from the AZT-resistant HIV-1 variant failed to show resistance to AZT 5'-triphosphate.