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Identification and characterization of human immunodeficiency virus type 1 mutations responsible for resistance to 2',3"-dideoxyinosine, 2',3"- dideoxycytidine and 2',3"-dideoxy-3'-thiacytidine

McGill University
Publication Date
  • Biology
  • Molecular.
  • Biology
  • Genetics.
  • Health Sciences
  • Pharmacology.


The recombinant K65R mutant RT had selectively altered catalytic efficiency and recognition of dNTP substrates/ddNTP inhibitors in steady-state kinetic assays. Furthermore, by employing chain elongation/dNTP incorporation assays, using a HIV-1 genome-derived RNA template and either deoxyoligonucleotide or tRNA$ rm sp{lys3}$ as primers, it was shown that this mutant RT had decreased frequency and altered patterns of chain termination in the presence of a variety of nucleoside analog triphosphates. Thus, both altered recognition of dNTPs/ddNTPs and decreased chain termination effect of ddNTPs constitute aspects of the molecular basis of HIV-1 resistance.

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