Abstract: In a series of experiments, we have shown that (i) a cloned virus with an engineered Leu74Val mutation in RT was attenuated for replication; (ii) a Val-to-Leu revertant of Leu74Val in the pNL4-3 background replicated with an efficiency similar to that of the wild-type virus; (iii) when two isolates from the same patient were compared, a clinical isolate containing mutations Leu74Val and Thr215Tyr was attenuated for replication compared to one in which the Thr215Tyr mutation alone was present; and (iv) the viruses with the Leu74Val mutation showed an 11% loss of fitness in a single passage compared to the wild-type and a mutant virus containing a Lys70Arg mutation.
Pre-steady-state kinetic characterization of wild type and 3'-azido-3'-deoxythymidine (AZT) resistant human immunodeficiency virus type 1 reverse transcriptase: implication of RNA directed DNA polymerization in the mechanism of AZT resistance.
Abstract: A detailed pre-steady-state kinetic analysis of wild type and the clinically important AZT resistant mutant (D67N, K70R, T215Y, K219Q) HIV-1 reverse transcriptase was conducted to understand the mechanistic basis of drug resistance.
Zidovudine resistance is suppressed by mutations conferring resistance of human immunodeficiency virus type 1 to foscarnet.
Abstract: Highly PFA-resistant HIV- 1 strains were hypersusceptible to AZT; conversely, AZT-resistant strains with M41L and T215Y; M41L, L210W, and T215Y; or M41L, D67N, K70R, and T215Y mutations were 2.2- to 2.5-fold hypersusceptible to PFA.
Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations.
Abstract: Analysis of virion-associated reverse transcriptase activity indicated that the Lys70Arg mutation resulted in an enzyme with 2- to 4-fold decreased susceptibility to ddATP.
Abstract: Drug susceptibility assays on the virus with Lys70Arg mutation showed a marginal decrease in susceptibility to ddl (1.5- to 2-fold) and about 4- to 6-fold decrease in susceptibility to AZT.
Abstract: Statistical analysis of the inhibitory concentration for RT activity between pNL4-3 and mutant Lys70Arg viruses obtained in three independent RT inhibition assays was significant (P = 0.05) by student t test paired analysis.
Abstract: The AZT-associated Lys70Arg mutation results in an RT enzyme with decreased susc
Effects of zidovudine-selected human immunodeficiency virus type 1 reverse transcriptase amino acid substitutions on processive DNA synthesis and viral replication.
Abstract: Certain amino acid substitutions in the reverse transcriptase (RT), including D67N, K70R, T215Y, and K219Q, cause high-level resistance of human immunodeficiency virus type 1 (HIV-1) to zidovudine (3'-azidothymidine; AZT) and appear to approximate the template strand of the enzyme-template-primer complex in structural models.
Abstract: The results confirm that RT mutations D67N, K70R, T215Y, and K219Q affect an enzyme-template-primer interaction in vitro and suggest that such substitutions may affect HIV-1 pathogenesis during therapy by increasing viral replication capacity in cells stimulated after i
Evolution of zidovudine resistance-associated genotypes in human immunodeficiency virus type 1-infected patients.
PMID: 8624762
1996
Journal of acquired immune deficiency syndromes and human retrovirology
Abstract: In p87, K70R also appeared at 4 months, but T215Y and K219Q were not observed until 18 months and M41L not at all.
Abstract: In patient p74, K70R appeared after 4 months, T215Y at 5.5 months, and M41L at 13 months.
Development of zidovudine resistance mutations in patients receiving prolonged didanosine monotherapy.
PMID: 7594706
1995
The Journal of infectious diseases
Abstract: However, after prolonged ddI monotherapy, mutations associated with zidovudine resistance (M41L, D67N, K70R, and/or T215Y) were detected in HIV-1 isolates from both patients.
Sensitivity of HIV-1 reverse transcriptase and its mutants to inhibition by azidothymidine triphosphate.
Abstract: A reverse transcriptase containing a set of four mutations (D67N, K70R, T215Y, K219Q) known to cause resistance to AZT in cell culture assays has a ratio of incorporation that is 0.77 +/- 0.03 times the ratio for the wild-type reverse transcriptase opposite one specific template adenosine.
Zidovudine treatment results in the selection of human immunodeficiency virus type 1 variants whose genotypes confer increasing levels of drug resistance.
PMID: 7509370
1994
The Journal of general virology
Abstract: High level resistance to 3'-azido-3'-deoxythymidine (AZT, zidovudine or Retrovir) is conferred by the presence of four or five mutations (Met-41-->Leu; Asp-67-->Asn; Lys-70-->Arg; Thr-215-->Tyr or Phe; Lys-219-->Gln) in the human immunodeficiency virus (HIV) reverse transcriptase.
Biochemical and genetical analysis of AZT-resistant HIV-mutants.
HIV mutation literature information.
PMID: 
1997
Journal of virology
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