Increased polymerase fidelity of the 3TC-resistant variants of HIV-1 reverse transcriptase
- 15 August 1997
- journal article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 25 (16) , 3212-3217
- https://doi.org/10.1093/nar/25.16.3212
Abstract
Human immunodeficiency virus type 1 (HIV-1) variants with resistance mutations in the reverse transcriptase (RT) gene appear during drug therapy with the nucleo- side analogue 24,34-dideoxy-34-thiacytidine (3TC). These 3TC-resistant RT variants have a single point mutation that changes the 184Met residue into either Val or Ile. Both codon 184 variants are frequently observed in 3TC-treated patients and can also be selected in cell culture infections. We demonstrated previously that the 184Ile and 184Val RT enzymes exhibit a processivity defect in in vitro assays, with 184Ile being the least processive enzyme (Met(wt) > Val > Ile). In this study, we measured the polymerase fidelity of the wild-type (184Met) and 3TC-resistant RT enzymes (184Ile and 184Val) on DNA and RNA templates. Both virion- extracted and Escherichia coli-expressed recombinant RT enzymes were used to measure the nucleotide misinsertion and mispair extension efficiencies. The 3TC-resistant enzymes were more accurate than the wild-type RT protein in both type of assays. The order of accuracy observed for the codon 184 variants (Ile > Val > Met(wt)) may suggest an inverse correlation between the fidelity and processivity properties of these enzymes.Keywords
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