Correlation between viral resistance to zidovudine and resistance at the reverse transcriptase level for a panel of human immunodeficiency virus type 1 mutants.
Using a large panel of human immunodeficiency virus type 1 site-directed mutants, we have observed a higher correlation than has previously been demonstrated between zidovudine (AZT)-triphosphate resistance data at the reverse transcriptase (RT) level and corresponding viral AZT resistance. This enhanced-resistance effect at the RT level was seen with ATP and to a lesser extent with PP(i) when ATP was added at physiological concentrations. The ATP-dependent mechanism (analogous to pyrophosphorolysis) appears to be dominant in the mutants bearing the D67N and K70R or 69 insertion mutations, whereas the Q151M mutation seems independent of ATP for decreased binding to AZT-triphosphate.
Lennerstrand
J
J
Virco UK, Ltd., Cambridge CB4 0GA, United Kingdom. johan.lennerstrand@impi.ki.se
Hertogs
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K
Stammers
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DK
Larder
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D000255:Adenosine Triphosphate / Q000378:metabolism; D019380:Anti-HIV Agents / Q000494:pharmacology*; D054306:Dideoxynucleotides; D004352:Drug Resistance, Microbial; D006160:Guanosine Triphosphate / Q000378:metabolism; D054303:HIV Reverse Transcriptase / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013942:Thymine Nucleotides / Q000494:pharmacology*; D015215:Zidovudine / Q000031:analogs & derivatives / Q000494:pharmacology*
D019380:Anti-HIV Agents; D054306:Dideoxynucleotides; D018894:Reverse Transcriptase Inhibitors; D013942:Thymine Nucleotides; D015215:Zidovudine; C052873:zidovudine triphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D054303:HIV Reverse Transcriptase