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Sökning: WFRF:(Larder D)

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  • Lennerstrand, Johan, et al. (författare)
  • Biochemical mechanism of human immunodeficiency virus type 1 reverse transcriptase resistance to stavudine
  • 2001
  • Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 45:7, s. 2144-2146
  • Tidskriftsartikel (refereegranskat)abstract
    • We have found a close correlation between viral stavudine (d4T) resistance and resistance to d4T-triphosphate at the human immunodeficiency virus type 1 reverse transcriptase (RT) level. RT from site-directed mutants with 69S-XX codon insertions and/or conventional zidovudine resistance mutations seems to be involved in an ATP-dependent resistance mechanism analogous to pyrophosphorolysis, whereas the mechanism for RT with the Q151M or V75T mutation appears to be independent of added ATP for reducing binding to d4T-triphosphate.
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  • Lennerstrand, Johan, et al. (författare)
  • Correlation between viral resistance to zidovudine and resistance at the reverse transcriptase level for a panel of human immunodeficiency virus type 1 mutants
  • 2001
  • Ingår i: Journal of Virology. - 0022-538X .- 1098-5514. ; 75:15, s. 7202-7205
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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