Mechanisms of HIV-1 nucleoside reverse transcriptase inhibitor resistance: Is it all figured out?

Current Opinion in Investigational Drugs

Volumn 2, Issue 3, 2001, Pages 335-339

  Naeger, L K ^a   Miller, M D ^a  

^a GILEAD SCIENCES   (United States)

Author keywords

ATP mediated unblocking; HIV; Mutation; NRTI; Pyrophosphorolysis; Resistance; Reverse transcriptase

Indexed keywords

ADENOSINE TRIPHOSPHATE; DIDANOSINE; LAMIVUDINE; PYROPHOSPHATE; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; STAVUDINE; TENOFOVIR; ZALCITABINE; ZIDOVUDINE;

ANTIBIOTIC RESISTANCE; ANTIBIOTIC SENSITIVITY; CROSS RESISTANCE; DRUG BINDING; DRUG DISTRIBUTION; DRUG SCREENING; DRUG STRUCTURE; ENZYME SUBSTRATE COMPLEX; GENE MUTATION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LYSIS; MICHAELIS CONSTANT; NONHUMAN; REVIEW; RNA TRANSLATION; STRUCTURE ACTIVITY RELATION;

ADENINE; ADENOSINE TRIPHOSPHATE; ANTI-HIV AGENTS; DRUG RESISTANCE, MICROBIAL; HIV-1; MUTATION; ORGANOPHOSPHORUS COMPOUNDS; PHOSPHONIC ACIDS; REVERSE TRANSCRIPTASE INHIBITORS; RNA-DIRECTED DNA POLYMERASE; STAVUDINE; ZIDOVUDINE;

EID: 0035061595     PISSN: 09678298     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (52)

1. Touching the heart of HIV-1 drug resistance: The fingers close down on the dNTP at the polymerase active site
2. Endogenous reverse transcription assays reveal high-level resistance to the triphosphate of (-)2′-dideoxy-3′-thiacytidine by mutated M184V human immunodeficiency virus type 1
3. Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with β-branched amino acids
4. Mechanism of resistance of human immunodeficiency virus type 1 to 2′,3′-dideoxyinosine
5. Resistance to ddl and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase
6. The K65R mutant reverse transcriptase of HIV-1 cross resistant to 2′,3′-dideoxycytidine, 2′,3′-dideoxy-3′-thiacytidine, and 2′,3′-dideoxyinosine shows reduced sensitivity to specific dideoxynucleoside triphosphate inhibitors in vitro
7. In vitro selection and characterization of HIV-1 with reduced susceptibility to PMPA
8. Enzymatic characterization of human immunodeficiency virus type 1 reverse transcriptase resistant to multiple 2′,3′-dideoxynucleoside 5′-triphosphates
9. Multiple mutations in HIV-1 reverse transcriptase confer high-level resistance to zidovudine (AZT)
10. Fifth mutation in human immunodeficiency virus type 1 reverse transcriptase contributes to the development of high-level resistance to zidovudine
11. Characterization of reverse transcriptase activity and susceptibility to other nucleosides of AZT-resistant variants of HIV-1. Results from the Canadian AZT Multicentre Study
12. Biochemical studies on the reverse transcriptase and RNase H activities from human immunodeficiency virus strains resistant to 3′-azido-3′-deoxythymidine
13. Sensitivity of HIV-1 reverse transcriptase and its mutants to inhibition by azidothymidine triphosphate
14. 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
15. Single-step kinetics of HIV-1 reverse transcriptase mutants responsible for virus resistance to nucleoside inhibitors zidovudine and 3-TC
16. 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
17. Enhanced binding of azidothymidine-resistant human immunodeficiency virus 1 reverse transcriptase to the 3′-azido-3′-deoxythymidine 5′-monosphosphate-terminated primer
18. On the fidelity of DNA replication. Lack of exodeoxyribonuclease activity and error-correcting function in avian myeloblastosis virus DNA polymerase
19. The accuracy of reverse transcriptase from HIV-1
20. Kinetic mechanism of the DNA-dependent DNA polymerase activity of human immunodeficiency virus reverse transcriptase
21. Human immunodeficiency virus reverse transcriptase. A kinetic analysis of RNA-dependent and DNA-dependent DNA polymerization
22. Metabolism of inorganic pyrophosphate (PPi)
23. Luminescent immobilized enzyme test systems for inorganic pyrophosphate: Assays using firefly luciferase and nicotinamide-mononucleotide adenylyl transferase or adenosine-5′-triphosphate sulfurylase
24. Unblocking of chain-terminated primer by HIV-1 reverse transcriptase through a nucleotide-dependent mechanism
25. A mechanism of AZT resistance: An increase in nucleotide-dependent primer unblocking by mutant HIV-1 reverse transcriptase
26. Novel mutation (V75T) in human immunodeficiency virus type 1 reverse transcriptase confers resistance to 2′,3′-didehydro-2′,3′-dideoxythymidine in cell culture
27. Genotypic and phenotypic analysis of human immunodeficiency virus type 1 isolates from patients on prolonged stavudine therapy
28. Stavudine resistance: An update on susceptibility following prolonged therapy
29. Emergence of zidovudine resistance in HIV-infected patients receiving stavudine
30. Emergence of zidovudine and multidrug-resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus didanosine combination therapy. STADI Group
31. Lack of emergence of genotypic resistance to stavudine after 2 years of monotherapy
32. Mutations in retroviral genes associated with drug resistance: 2000-2001 update
33. Susceptibilities of zidovudine-susceptible and -resistant human immunodeficiency virus isolates to antiviral agents determined by using a quantitative plaque reduction assay
34. A novel phenotypic drug susceptibility assay for human immunodeficiency virus type 1
35. A rapid method for simultaneous detection of phenotypic resistance to inhibitors of protease and reverse transcriptase in recombinant human immunodeficiency virus type 1 isolates from patients treated with antiretroviral drugs
36. Human immunodeficiency virus-infected persons with mutations conferring resistance to zidovudine show reduced virologic responses to hydroxyurea and stavudine-lamivudine
37. Differential removal of thymidine nucleotide analogues from blocked DNA chains by human immunodeficiency virus reverse transcriptase in the presence of physiological concentrations of 2′-deoxynucleoside triphosphates
38. Standardized peripheral blood mononuclear cell culture assay for determination of drug susceptibilities of clinical human immunodeficiency virus type 1 isolates. The RV-43 Study Group, the AIDS Clinical Trials Group Virology Committee Resistance Working Group
39. Recombinant virus assay: A rapid, phenotypic assay for assessment of drug susceptibility of human immunodeficiency virus type 1 isolates
40. Tenofovir is less susceptible to pyrophosphorolysis and nucleotide-dependent chain-terminator removal than zidovudine or stavudine, XIV International Roundtable on Nucleosides, Nuceotides, and Their Biological Applications
41. Tenofovir (PMPA) is less efficiently removed through pyrophosphorolysis and dinucleotide polyphosphate synthesis than zidovudine (AZT) by HIV-1 wild-type RT and RT mutants
42. The M184V mutation in the reverse transcriptase of human immunodeficiency virus type 1 impairs rescue of chain-terminated DNA synthesis
43. High-level resistance to (-)-enantiomeric 2′-deoxy-3′-thiacytidine in vitro is due to one amino acid substitution in the catalytic site of the human immunodeficiency virus type 1 reverse transcriptase
44. 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
45. Potential mechanism for sustained antiretroviral efficacy of AZT-3TC combination therapy
46. Altered drug susceptibility of HIV-1 RT mutants containing M184V and zidovudine-resistance mutations: Analysis of RT processivity, viral replication, and chain-terminator removal
47. Role of a dipeptide insertion between codons 69 and 70 of HIV-1 reverse transcriptase in the mechanism of AZT resistance
48. Mutational analysis of Lys65 of HIV-1 reverse transcriptase
49. Functional analysis of amino acid residues constituting the dNTP binding pocket of HIV-1 reverse transcriptase
50. Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: Implications for drug resistance
51. Physiological concentrations of purines and pyrimidines
52. Analysis of nucleotide pools in animal cells