Abstract: The D67N/K70R mutations result in a significantly increased rate of RT-catalyzed pyrophosphorolysis at physiological levels of pyrophosphate, which leads to a decrease in the extent of AZT chain termination of nascent viral DNA.
Abstract: While this resistance could be unequivocally correlated with multiple mutations in HIV reverse transcriptase (D67N, K70R, T215F/Y, K219Q), the mechanism or phenotype for this resistance has remained obscure for more than a decade, despite active investigation.
Fast genotypic detection of drug resistance mutations in the HIV-1 reverse transcriptase gene of treatment-naive patients.
Abstract: Mutation K70R (resistance to zidovudine) was found in 8 patients, M41L (resistance to zidovudine) in 5 patients, M184V/I (resistance to ddI/ddC/3TC) in 2 patients, and T215Y/F (resistance to zidovudine) in 4 patients.
Phenotypic mechanism of HIV-1 resistance to 3'-azido-3'-deoxythymidine (AZT): increased polymerization processivity and enhanced sensitivity to pyrophosphate of the mutant viral reverse transcriptase.
Abstract: The D67N/ Abstract: The D67N/K70R/T215F/K219Q mutant showed an increased rate of pyrophosphorolysis (the reverse reaction of DNA synthesis) of chain-terminated DNA; this enhanced pyrophosphorolysis was due to the D67N/K70R mutations.
Abstract: The D67N/K70R/T215F/K219Q mutant showed increased DNA polymerase processivity; this resulted from decreased template/primer dissociation from RT, and was due to the T215F/K219Q mutations.
Implication of the tRNA initiation step for human immunodeficiency virus type 1 reverse transcriptase in the mechanism of 3'-azido-3'-deoxythymidine (AZT) resistance.
Abstract: A pre-steady-state kinetic analysis was used to examine the binding and incorporation of 2'-deoxythymidine 5'-triphosphate (dTTP) and 3'-azido-3'-deoxythymidine 5'-triphosphate (AZTTP) by wild-type HIV-1 reverse transcriptase and a clinically important AZT-resistant mutant form of the enzyme (D67N, K70R, T215Y, K219Q) utilizing a physiologically relevant RNA 18-mer/RNA 36-mer primer-template substrate.
Enhanced binding of azidothymidine-resistant human immunodeficiency virus 1 reverse transcriptase to the 3'-azido-3'-deoxythymidine 5'-monophosphate-terminated primer.
PMID: 9603976
1998
The Journal of biological chemistry
Abstract: Human immunodeficiency virus type 1 is resistant to 3'-azido-3'-deoxythymidine (AZT) when four amino acid substitutions (D67N, K70R, T215F, and K219Q) are present simultaneously in its reverse transcriptase.
Relative replicative fitness of zidovudine-resistant human immunodeficiency virus type 1 isolates in vitro.
Abstract: The order of relative fitness was wild type > K70R >> T215Y = M41L+T215Y > M41L.
Abstract: These variants were engineered to contain commonly observed zidovudine resistance mutations in the HIV-1 reverse transcriptase (M41L, K70R, T215Y, and M41L+T215Y).
Switch to unusual amino acids at codon 215 of the human immunodeficiency virus type 1 reverse transcriptase gene in seroconvertors infected with zidovudine-resistant variants.
Abstract: Two patients had both the D67N and the K70R amino acid substitutions; reversion to the wild type was seen at both positions in one of these patients and at codon 70 in the other one.
Additional mutations detected in sequential HIV-1 isolates from ZDV-treated patients.
Abstract: The mutation Thr215Tyr was not observed in a case of highly resistant virus (ZDV IC50 > 6.25 microM), while the mutation Lys70Arg was found in either resistant or sensitive ones.
Single-step kinetics of HIV-1 reverse transcriptase mutants responsible for virus resistance to nucleoside inhibitors zidovudine and 3-TC.
Abstract: Two mutants of HIV-1 reverse transcriptase (RT) associated with high-level resistance of the virus to AZT (RT-AZT: D67N, K70R, T215Y, K219Q, and M41L) or 3-TC (RT-3TC: M184V) were expressed in Escherichia coli and purified.
HIV mutation literature information.
PMID: 
1999
Journal of acquired immune deficiency syndromes (1999)
Browser Board
Co-occurred Entities
Filtrator
ViMRT