A Mechanism of AZT Resistance
1999; Elsevier BV; Volume: 4; Issue: 1 Linguagem: Inglês
10.1016/s1097-2765(00)80185-9
ISSN1097-4164
AutoresPeter R. Meyer, S. Matsuura, A. Mohsin Mian, Antero G. So, Walter A. Scott,
Tópico(s)HIV/AIDS Research and Interventions
ResumoMutations in HIV-1 reverse transcriptase (RT) give rise to 3′-azido-3′-deoxythymidine (AZT) resistance by a mechanism that has not been previously reproduced in vitro. We show that mutant RT has increased ability to remove AZTMP from blocked primers through a nucleotide-dependent reaction, producing dinucleoside polyphosphate and extendible primer. In the presence of physiological concentrations of ATP, mutant RT extended 12% to 15% of primers past multiple AZTMP termination sites versus less than 0.5% for wild type. Although mutant RT also unblocked ddAMP-terminated primers more efficiently than wild-type RT, the removal of ddAMP was effectively inhibited by the next complementary dNTP (IC50 ≈ 12 μM). In contrast, the removal of AZTMP was not inhibited by dNTPs except at nonphysiological concentrations (IC50 > 200 μM).
Referência(s)