Increased drug susceptibility of HIV-1 reverse transcriptase mutants containing M184V and zidovudine-associated mutations: Analysis of enzyme processivity, chain-terminator removal and viral replication

Antiviral Therapy

Volumn 6, Issue 2, 2001, Pages 115-126

  Naeger, L K ^a   Margot, N A ^a   Miller, M D ^a  

^a GILEAD SCIENCES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADEFOVIR; RNA DIRECTED DNA POLYMERASE; TENOFOVIR; ZIDOVUDINE;

ARTICLE; BINDING AFFINITY; DRUG BINDING; DRUG MECHANISM; DRUG SENSITIVITY; ENZYME ACTIVITY; ENZYME ANALYSIS; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; PRIORITY JOURNAL; VIRUS MUTANT; VIRUS MUTATION; VIRUS REPLICATION;

ANTI-HIV AGENTS; DNA, VIRAL; DRUG RESISTANCE, MICROBIAL; DRUG THERAPY, COMBINATION; HIV INFECTIONS; HIV-1; HIV-1 REVERSE TRANSCRIPTASE; HUMANS; MUTAGENESIS, SITE-DIRECTED; MUTATION; PEPTIDE CHAIN TERMINATION, TRANSLATIONAL; RECOMBINANT PROTEINS; VIRAL LOAD; VIRUS REPLICATION; ZIDOVUDINE;

EID: 0034947293     PISSN: 13596535     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (45)

1. Zidovudine resistance is suppressed by mutations conferring resistance of human immunodeficiency virus type 1 to foscarnet
2. High-level resistance to (-) enantiomeric 2′-deoxy-3′-thiacytidine in vitro is due to one amino acid substitution in the catalytic site of human immunodeficiency virus type 1 reverse transcriptase
3. Potential mechanism for sustained antiretroviral efficacy of AZT-3TC combination therapy
4. Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3′-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase
5. Human immunodeficiency virus type 1 expressing the lamivudine-associated M184V mutation in reverse transcriptase shows increased susceptibility to adefovir and decreased replication capability in vitro
6. 5-Phosphoribosyl 1-pyrophosphate synthetase converts the acyclic nucleoside phosphonates 9-(3-hydroxy-2-phosphonylmethoxypropyl) adenine and 9-(2-phosphonylmethoxyethyl)adenine directly to their antivirally active diphosphate derivatives
7. Metabolic pathways for activation of the antiviral agent 9-(2-phosphonylmethoxyethyl)adenine in human lymphoid cells
8. Potent inhibition of human immunodeficiency virus and herpes simplex virus type 1 by 9-(2-phosphonylmethoxyethyl)adenine (PMEA) in primary macrophages is determined by drug metabolism, nucleotide pools and cytokines
9. Emergence of human immunodeficiency virus type 1 variants with resistance to multiple dideoxynucleosides in patients receiving therapy with dideoxynucleosides
10. Intracellular metabolism and mechanism of anti-retrovirus action of 9-(2-phosphonylmethoxy) adenine, a potent anti-human immunodeficiency virus compound
11. A double-blind, placebo-controlled study of tenofovir disoproxil fumarate (TDF) for the treatment of HIV infection
12. The safety and efficacy of PMPA prodrug monotherapy: Preliminary results of a phase I/II dose-escalation study
13. Safety, pharmacokinetics, and antiretroviral activity of intravenous 9-[2-(R)-(phosphonomethoxy)propyl]adenine, a novel anti-human immunodeficiency virus (HIV) therapy, in HIV-infected adults
14. Efficacy and safety of adefovir dipivoxil with antiretroviral therapy: A randomized controlled trial
15. The safety and efficacy of adefovir dipivoxil, a novel anti-human immunodeficiency virus (HIV) therapy, in HIV-infected adults: A randomized, double-blind, placebo-controlled trial
16. A placebo-controlled phase I/II study of adefovir dipivoxil in patients with chronic hepatitis B virus infection
17. Loss of serum HBV DNA and HBeAg and seroconversion following short-term (12 weeks) adefovir dipivoxil therapy in chronic hepatitis B: Two placebo-controlled phase II studies
18. Adefovir dipivoxil (bis-POM-PMEA) therapy significantly decreases HIV RNA in patients with high-level zidovudine/lamivudine-resistant HIV
19. Adefovir dipivoxil (bis-POM PMEA) therapy significantly decreased HIV RNA in patients with high-level AZT/3TC-resistant HIV
20. Adefovir dipivoxil is active in patients with 3TC or AZT/3TC resistant HIV
21. Unblocking of chain-terminated primer by HIV-1 reverse transcriptase through a nucleotide-dependent mechanism
22. 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
23. HIV-1 drug susceptibility determination by using recombinant viruses generated from patient sera tested in a cell-killing assay
24. Comparative kinetic analyses of interaction of inhibitors with rauscher murine leukemia virus and human immunodeficiency virus reverse transcriptases
25. Identification of a mutation of Codon 65 in the IKKK motif of reverse transcriptase that encodes human immunodeficiency virus resistance to 2′,3′-dideoxycytidine and 2′,3′-dideoxy-3′-thiacytidine
26. RNase H activity associated with bacterially expressed reverse transcriptase of human T-cell tropic virus III/lymphadenopathy-associated virus
27. Kinetic interaction of the diphosphates of 9-(2-phosphonylmethoxyethyl)adenine and other anti-HIV active purine congeners with HIV reverse transcriptase and human DNA polymerases alpha, beta, and gamma
28. Comparison of deoxyoligonucleotide and tRNA(Lys-3) as primers in an endogenous human immunodeficiency virus-1 in vitro reverse transcription/template-switching reaction
29. Human immunodeficiency virus type 1 reverse transcriptase expressing the K70E mutation exhibits a decrease in specific activity and processivity
30. Expression of the catalytic subunit (UL54) and the accessory protein (UL44) of human cytomegalovirus DNA polymerase in a coupled in vitro transcription/translation system
31. The K65R mutation confers increased DNA polymerase processivity to HIV-1 reverse transcriptase
32. Biochemical studies on the reverse transcriptase and Rnase H activities from human immunodeficiency virus strains resistant to 3′-azido-3′-deoxythymidine
33. Inhibition of HIV-1 reverse transcriptase by a quinazolinone and comparison with inhibition by pyridinones. Differences in the rates of inhibitor binding and in synergistic inhibition with nucleoside analogs
34. Single-step kinetics of HIV-1 reverse transcriptase mutants responsible for virus resistance to nucleoside inhibitors zidovudine and 3TC
35. Template-driven pausing of DNA synthesis by HIV-1 reverse transcriptase during polymerization of HIV-1 sequences in vitro
36. Effects of zidovudine-selected human immunodeficiency virus type 1 reverse transcriptase amino acid substitutions on processive DNA synthesis and viral replication
37. A mechanism of AZT resistance: An increase in nucleotide-dependent primer unblocking by mutant HIV-1 reverse transcriptase
38. Enhanced binding of azidothymidine-resistant Human Immunodeficiency Virus 1 reverse transcriptase to the 3′-azido-′deoxythymidine 5′-monophosphate-terminated primer
39. Metabolism of inorganic pyrophosphate (PPi)
40. Luminescent immobilized enzyme test systems for inorganic pyrophosphate: Assays using firefly luciferase and nicotinamide-mononucleotide adenylyl transferase or adenosine-5′-triphosphate sulfurylase
41. Removal of chain terminators from blocked primers by HIV-1 reverse transcriptase: Implications for drug resistance
42. Physiological concentrations of purines and pyrimidines
43. The M184V mutation in the reverse transcriptase of human immunodeficiency virus type 1 impairs rescue of chain-terminated DNA synthesis
44. Reduced replication of 3TC-resistant HIV-1 variants in primary cells due to a processivity defect of the reverse transcriptase enzyme
45. Rapid changes in human immunodeficiency virus type I RNA load and appearance of drug-resistant virus populations in persons treated with lamivudine (3TC)