Stability of human immunodeficiency virus to azidothymidine. II. Kinetic characteristics of "AZT-resistant" mutant forms of reverse transcriptase

Prolonged treatment of AIDS patients with azidothymidine results in the development of resistance to the drug which correlates with the appearance of point mutations in the reverse transcriptase (RT) coding region within the HIV-1 pol gene. Kinetic studies of interactions of wild type RT and its mut...

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Bibliographic Details
Published inBiokhimiia (Moscow, Russia) Vol. 61; no. 1; p. 142
Main Authors Pokholok, D K, Gudima, S O, Memelova, L V, Esipov, D S, Rechinskiĭ, V O, Kochetkov, S N
Format Journal Article
LanguageRussian
Published Russia (Federation) 01.01.1996
Subjects
Drug Resistance, Microbial - genetics
Genes, pol
HIV Reverse Transcriptase
HIV-1 - drug effects
HIV-1 - enzymology
Kinetics
Mutation
RNA-Directed DNA Polymerase - genetics
RNA-Directed DNA Polymerase - metabolism
Substrate Specificity
Templates, Genetic
Zidovudine - pharmacology
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Summary:Prolonged treatment of AIDS patients with azidothymidine results in the development of resistance to the drug which correlates with the appearance of point mutations in the reverse transcriptase (RT) coding region within the HIV-1 pol gene. Kinetic studies of interactions of wild type RT and its mutants harbouring the above mutations with substrates and azidothymidine 5'-triphosphate (AZTTP) have been carried out. The complete mutant containing all the above described mutations possess the highest resistance on all the templates tested. Significant increases in resistance for mutants 67,70,215 and 67,215 on all the templates have also been observed. Inhibition of mutant enzymes by AZTTP depends on the template used.
ISSN:0320-9725