Biochemical mechanisms involved in overcoming HIV resistance to nucleoside inhibitors of reverse transcriptase

Drug Resistance Updates

Volumn 3, Issue 1, 2000, Pages 30-38

  Götte, Matthias ^a   Wainberg, Mark A ^a  

^a MCGILL UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ABACAVIR; ADEFOVIR; DELAVIRDINE; DIDANOSINE; EFAVIRENZ; FOSCARNET; LAMIVUDINE; NEVIRAPINE; RNA DIRECTED DNA POLYMERASE INHIBITOR; STAVUDINE; ZALCITABINE; ZIDOVUDINE;

AMINO ACID SUBSTITUTION; COMPLEX FORMATION; DRUG EFFECT; DRUG MECHANISM; ENZYME INHIBITION; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; NONHUMAN; PRIORITY JOURNAL; REVIEW; VIRUS MUTATION; VIRUS RESISTANCE;

EID: 0034144024     PISSN: 13687646     EISSN: None     Source Type: Journal    
DOI: 10.1054/drup.2000.0126     Document Type: Article

References (87)

1. Telesnitsky A, Goff SP. Strong-stop strand transfer during reverse transcription. In: Skalka AM, Goff SP, eds Reverse Transcriptase; Cold Spring Harbor Laboratory Press, New York 1993; 49-83.
2. Schinazi RF, Larder BA, Mellors JW. Mutations in retroviral genes associated with drug resistance. Int Antiviral News 1996; 4: 95-107.
3. Bebenek K, Kunkel TA. The fidelity of retroviral reverse transcriptases. In: Skalka AM, Goff SP, eds Reverse Transcriptase. Cold Spring Harbor Laboratory Press, New York 1993; 85-102.
4. di Marzo Veronese F, Copeland TD, DeVico AL, et al. Characterization of highly immunogenic p66/p51 as reverse transcriptase of HTLV-III/LAV. Science 1986; 231: 1289-1291.
5. Le Grice SF, Naas T, Wohlgensinger B, et al. Subunit selective mutagenesis indicates minimal polymerase activity in heterodimer-associated p51 HIV-I reverse transcriptase EMBO J 1991; 10: 3905-3911.
6. Kohlstaedt LA, Wang J, Friedman JM, et al. Crystal structure at 3.5 Å resolution of HIV-I reverse transcriptase complexed with an inhibitor. Science 1992; 256: 1783-1790.
7. Huang H, Chopra R, Verdine GL, et al. Structure of a covalently trapped catalytic complex of HIV-I reverse transcriptase: Implications for drug resistance. Science 1998; 282: 1669-1675.
8. Sarafianos SG, Das K, Ding J, et al. Touching the heart of HIV-I drug resistance: The fingers close down on the dNTP at the polymerase active site. Chem Biol 1999; 6: 137-146.
9. Jacobo-Molina A, Ding J, Nanni RG, et al. Crystal structure of human immunodeficiency virus type I reverse transcriptase complexed with double-stranded DNA at 3.0 Å resolution shows bent DNA. Proc Natl Acad Sci USA 1993; 90: 6320-6324.
10. Wöhrl BM, Moelling K. Interaction of HIV-I ribonuclease H with polypurine tract containing RNA-DNA hybrids. Biochemistry 1990; 29: 10141-10147.
11. Gopalakrishnan V, Peliska JA, Benkovic SJ. Human immunodeficiency virus type I: Spatial and temporal relationship between the polymerase and RNase H activities. Proc Natl Acad Sci USA 1992; 89: 10763-10767.
12. Götte M, Fackler S, Hermann T, et al. HIV reverse transcriptase-associated RNase H cleaves RNA/RNA in arrested complexs: Implications for the mechanism by which RNase H discriminates between RNA/RNA and RNA/DNA. EMBO J 1995; 14: 833-841.
13. Götte M, Maier G, Gross HJ, et al. Localization of the active site of HIV-I reverse transcriptase-associated RNase H domain on a DNA template using site-specific generated hydroxyl radicals. J Biol Chem 1998; 273: 10139-10146.
14. Götte M, Maier G, Mochi Onori A, et al. Temporal coordination between initiation of HIV(+)-strand DNA synthesis and primer removal. J Biol Chem 1999; 274: 11159-11169.
15. Panganiban AT, Fiore D. Ordered interstrand and intrastrand DNA transfer during reverse transcription. Science 1988; 241: 1064-1069.
16. Hu WS, Temin HM. Retroviral recombination and reverse transcription. Science 1990; 250: 1227-1233.
17. Peliska JA, Benkovic SJ. Mechanism of DNA strand transfer reactions catalyzed by HIV-I reverse transcriptase. Science 1992; 258: 1112-1118.
18. van Wamel JL, Berkhout B. The first strand transfer during HIV-I reverse transcription can occur either intramolecular or intermolecular.Virology 1998; 244: 245-251.
19. Huber HE, Richardson CC. Processing of the primer for plus strand DNA synthesis by human immunodeficiency virus I reverse transcriptase. J Biol Chem 1990; 265: 10565-10573.
20. Charneau P,Alizon M, Clavel, F.A second origin of DNA plus-strand synthesis is required for optimal human immunodeficiency virus replication. J Virol 1992; 66: 2814-2820.
21. Fuentes GM, Rodriguez - Rodriguez L, Fay PJ, et al. Use of an oligoribonucleotide containing the polypurine tract sequence as a primer by HIV reverse transcriptase.J Biol Chem 1995; 270: 28169-2876.
22. Klarmann GJ,Yu H, Chen X, et al. Discontinuous plus-strand DNA synthesis in human immunodeficiency virus-type I-infected cells and in a partially reconstituted cell-free system. J Virol 1997; 71: 9259-9269.
23. Guo J, Wu T, Bess J, et al. Actinomycin D inhibits human immunodeficiency virus type I minus-strand transfer in in vitro and endogenous reverse transcriptase assays. J Virol 1998; 72: 6716-6724.
24. Jeeninger RE, Huthoff HT, Gultyaev AP, et al. The mechanism of actinomycin D-mediated inhibition of HIV-I reverse transcription. Nucl Acid Res 1998; 26: 5472-5479.
25. Davis WR, Gabbara S, Hupe D, et al. Actinomycin D inhibition of DNA strand transfer reactions catalyzed by HIV-I reverse transcriptase and nucleocapsid protein. Biochemistry 1998; 37: 14213-14221.
26. Zhan X, Tan CK, Scott WA, et al. Catalytically distinct conformations of the ribonuclease H of HIV-I reverse transcrptase by substrate cleavage patterns and inhibition by azidothymidylate and N-ethylmaleimide. Biochemistry 1994; 33: 1366-1372.
27. Loya S, Gao HQ, Avidan O, et al. Subunit-specific mutagenesis of the cystein 280 residue of the reverse transcriptase of human immunodeficiency virus type I: Effects on sensitivity to a specific inhibitor of the RNase H activity. J Virol 1997; 71: 5668-5672.
28. Borkow G, Fletcher RS, Barnard J, et al. Inhibition of the ribonuclease H and DNA polymerase activities of HIV-I reverse transcriptase by N-(4-tert-butylbenzoyl)-2-hydroxy-l-naphtaldehyde hydrazone. Biochemistry 1997; 36: 3179-3185.
29. Gabbara S, Davis WR, Hupe L, et al. Inhibitors of strand transfer reactions catalyzed by HIV-I reverse transcriptase. Biochemistry 1999; 38: 13070-13076.
30. Smerdon SJ, Jaeger J, Wang J, et al. Structure of the binding site for nonnucleoside inhibititors of the reverse transcriptase of human immunodeficiency virus type I. Proc Nat Acad Sci USA 1994; 91: 3911-3915.
31. Ding J, Das K, Moereels H, et al. Structure of HIV-I RT/TIBO R 86183 complex reveals similarity in the binding of diverse non-nucleoside inhibitors. Nat Struct Biol 1995; 2: 407-415.
32. Spence RA, Kati WM.Anderson KS, et al. Mechanism of inhibition of HIV-I reverse transcriptase by nonnucleoside inhibitors. Science 1995; 267: 988-993.
33. Esnouf RM, Ren J, Hopkins AL, et al. Unique features in the structure of the complex between HIV-I reverse transcriptase and the bis(heteroaryl) piperazine (BHAP) U-90152 explain resistance for this nonnucleoside inhibitor. Proc Natl Acad Sci USA 1997; 94: 3984-3989.
34. Götte M,Arion D, Cellai L, et al. Effects of nucleoside and non-nucleoside analogue RT inhibitors on the initiation of HIV-I plus-strand DNA synthesis. Antiviral Therapy 1999; 4: 18-19, Abstract 23.
35. Fischl MA. Antiretroviral therapy in 1999 for antiretroviral-naïve individuals with HIV infection. AIDS 1999; 13: 49-59.
36. Gunthard HF, Wong JK, Ignacio CC, et al. Human immunodeficiency virus replication and genotypic resistance in blood and lymph nodes after a year of potent antiretroviral therapy. J Virol 1998; 72: 2422-8.
37. Finzi D, Blankson J, Siliciano JD, et al. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-I, even in patients on effective combination therapy. Nature Medicine 1999; 5: 512-517.
38. Wong JK, Hezareh M, Gunthard HF, Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science 1997; 278: 1291-1295.
39. Skalski V, Chang C-N, Dutschman G, et al. The biochemical basis for the differential anti-human immunodeficiency virus activity of two cis enantiomers of 2′, 3′-dideoxy-3′-thiacytidine. J Biol Chem 1993; 268: 23234-23238.
40. Boucher CAB, Cammack N, Schipper P, et al. 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 I reverse transcriptase. Antimicrob Agents Chemother 1993; 37: 2231-2234.
41. Gao Q, Gu Z, Parniak MA, et al. The same mutation that encodes low-level human immunodeficiency virus type I resistance to 2′,3′-dideoxyinosine and 2′,3′ 'dideoxycytidine confers high-level resistance to the (-)enantiomer of 2′,3′-dideoxy-3′-thiacytidine. Antimicrob Agents Chemother 1993; 37: 1390-1392.
42. Schinazi RF, Lloyd RM Jr, Nguyen MH, et al. Characterization of human immunodeficiency viruses resistant to oxathiolane-cytosine nucleosides. Antimicrob Agents Chemother 1993; 37: 875-881.
43. Tisdale M, Kemp SD, Parry NR, et al. Rapid in vitro selection of human immunodeficiency virus type I resistance to 3′-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase. Proc Natl Acad Sci USA 1993; 90: 5653-5656.
44. Back NK, Nijhuis M, Keulen W, et al. Reduced replication of 3TC-resistant HIV-I variants in primary cells due to a processivity defect of the reverse transcriptase enzyme. EMBO J 1996; 15: 4040-1049.
45. Sarafianos SG, Das K, Clark AD, et al. Lamivudine (3TC) resistance in HIV-I reverse transcriptase involves steric hindrance with beta-branched amino acids. Proc NatAcad Sci USA 1990; 96: 10027-10032.
46. Quan Y, Gu Z, Li X, et al. Mutated HIV-I MI84V reverse transcriptase displays resistance to the triphosphate of (-)2′,3′-dideoxy-3′-thiacytidine (3TC) in both endogenous and cell-free enzyme assays. J Virol 1996; 70: 5642-5645.
47. Krebs R, Immendörfer U, Thrall SH, et al. Single-step kinetics of HIV-I reverse transcriptase mutants responsible for virus resistance to nucleoside inhibitors zidovudine and 3-TC. Biochemistry 1997; 36: 10292-10300.
48. Feng JY,Anderson KS. Mechanistic studies examining the efficiency and fidelity of DNA synthesis by the 3TC-resistant mutant (184V) of HIV-I reverse transcriptase. Biochemistry 1999; 38: 9440-9448.
49. Lacey SF, Reardon JE, Furfine ES, et al. Biochemical studies on the reverse transcriptase and RNase H activities from human immunodeficiency virus strains resistant to 3′-azido-3′-deoxythymidine J Biol Chem 1992; 267: 15789-15794.
50. Larder BA, Kemp SD. Multiple mutations in HIV-I reverse transcriptase confer high level resistance to zidovudine (AZT). Science 1989; 246: 1155-1158.
51. Larder BA, Coates KE, Kemp SD. Zidovudine-resistant human immunodeficiency virus selected by passage in cell culture. J Virol 1991; 65: 5232-5236.
52. Larder BA, Darby G, Richman DD. HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. Science 1989; 243: 1731-1734.
53. Rooke R, Tremblay M, Soudeyns H, et al. Isolation of drug-resistant variants of HIV-I from patients on long-term zidovudine (AZT) therapy. AIDS 1989; 3: 411-415.
54. Gao Q, Gu Z, Parniak MA, et al. In vitro selection of variants of human immunodeficiency virus type I resistant to 3′-azido-3′-deoxythymidine and 2′,3′-dideoxyinosine. J Virol 1992; 66: 12-19.
55. Boucher CAB, O'Sullivan E, Mulder JW, et al. Ordered appearance of zidovudine (AZT) resistance mutations during treatment. J Infect Dis 1992; 165: 105-110.
56. Arion D, Kaushik N, McCormic S, et al. Phenotypic mechanism of HIV-I resistance to 3′-azido-3′ deoxythymidine (AZT): Increased polymerization processivity and enhanced sensitivity to pyrophosphate of the mutant viral reverse transcriptase. Biochemistry 1998; 37: 15908-15917.
57. Caliendo AM, Savara A,An D, et al. Effects of zidovudine-selected human immunodeficiency virus type I reverse transcriptase amino acid substitutions on processive DNA synthesis and viral replication. J Virol 1996; 70: 2146-2153.
58. Arts EJ, Wainberg MA. Mechanisms of nucleoside analog antiviral activity and resistance during human immunodeficiency virus reverse transcription. Antimicrob Agents Chemother 1996; 40: 527-540.
59. Arts EJ, Marois J-P, Gu Z, et al. Effects of 3′-deoxynucleoside 5′-triphosphate concentrations on chain termination by nucleoside analogs during human immunodeficiency virus type I reverse transcription of minus-strand strong-stop DNA. J Virol 1996; 70: 712-720.
60. Arts EJ, Quinones-Mateu ME, Albright JL, et al. 3′-azido-3′-deoxythymidine (AZT) mediates cross-resistance to nucleoside analogs in the case of AZT-resistant human immunodeficiency virus type I variants. J Virol 1998; 72: 4858-1865.
61. Arts EJ, Quinones-Mateu ME,Albright JL, et al. Mechanisms of clinical resistance by HIV-I variants to zidovudine and the paradox of reverse transcriptase sensitivity. Drug Resistance Updates 1998; 1: 21-28.
62. Meyer PR, Matsuura SE, Mian AM, et al. A mechanism of AZT resistance: An increase in nucleotide-dependent primer unblocking by mutant HIV-I reverse transcriptase. Mol Cell 1999; 43: 35-13.
63. Meyer PR, Matsuura SE, So AG, et al. Unblocking of chain-terminated primer by HIV-I reverse transcriptase through a nucleotide-dependent mechanism. Proc Natl Acad Sci USA 1998; 95: 13471-13476.
64. de Jong MD,Veenstra J, Stilianakis NI, et al. Host-parasite dynamics and outgrowth of virus containing a single K70R amino acid change in reverse transcriptase are responsible for the loss of human immunodeficiency virus type I RNA load suppression by zidovudine. Proc Natl Acad Sci USA 1996; 93: 5501-5506.
65. Götte M, Arion D, Parniak MA, et al. Mechanisms of HIV-I resistance to zidovudine and lamivudine. Antiviral Therapy 1999; 4: 18, Abstract 22.
66. Götte M, Arion D, Parniak MA, et al. The M184V mutation in the reverse transcriptase of the human immunodeficiency virus type I impairs rescue of chain-terminated DNA synthesis. J Virol (in press).
67. Schuurman R, Nijhuis M, Leeuwen RV, et al. Rapid changes in human immunodeficiency virus type I RNA load and appearance of drug-resistant virus populations in persons treated with lamivudine (3TC). J Infect Dis 1995; 171: 1411-1419.
68. Larder BA, Kemp SD, Harrigan PR. Potential mechanism for sustained antiretroviral efficacy of AZT-3TC combination therapy. Science 1995; 269: 696-699.
69. Smith RA, Klarmann GJ, Stray KM, et al. A new point mutation (P157S) in the reverse transcriptase of human immunodeficiency virus type I confers low-level resistance to (-)-beta-2′, 3′-dideoxy-3′-thiacytidine. Antimicrob Agents Chemother 1999; 43: 2077-2080.
70. Foli A, Sogocio KM, Anderson B, et al. In vitro selection and molecular characterization of human immunodeficiency virus type I with reduced sensitivity to 9-[2- (phosphonomethoxy)ethyl]adenine (PMEA). Antiviral Research 1996; 32: 91-98.
71. Gu Z, Salomon H, Cherrington JM, et al. The K65R mutation of human immunodeficiency virus type I reverse transcriptase encodes resistance to 9-(2-phosphonyl-methoxyethyl)adenine. Antimicrob Agents Chemother 1995; 38: 1888-1891.
72. Wainberg MA, Miller DM, Quany, et al. In vitro selection and characterization of HIV-I with reduced susceptibility to PMPA. Antiviral Therapy 1999; 4: 87-94.
73. St Clair MH, Martin JL, Tudor-Williams G, et al. Resistance to ddl and sensitivity to AZT induced by a mutation in HIV-I. Science 1991; 253: 1557-1559.
74. Larder BA. 3′-azido-3′-deoxythymidine resistance suppressed by a mutation conferring human immunodeficiency virus type I resistance to nonnucleoside reverse transcriptase inhibitors. Antimicrob Agents Chemother 1992; 36: 2664-2669.
75. Tachedjian G, Mellors J, Bazmi H, et al. Zidovudine resistance is suppressed by mutations conferring resistance of human immunodeficiency virus type I to foscarnet. J Virol 1996; 70: 7171-7181.
76. Byrnes VW, Emini EA, Schleif WA, et al. Susceptibilities of human immunodeficiency virus type I enzyme and viral variants expressing multiple resiostance-engendering amino acid substitutions to reverse transcriptase inhibitors. Antimicrob Agents Chemother 1994; 38: 1404-1407.
77. Borkow G,Arion D,Wainberg MA, et al. The thiocarboxanilide nonnucleoside inhibitor UC 781 restores antiviral activity of 3′-azido-3′-deoxythymidine (AZT) against AZT-resistant human immunodeficiency virus type I. Antimicrob Agents Chemother 1999; 43: 259-263.
78. Nijhuis M, Scuurman R, de Jong D, et al. Lamivudine resistant human immunodeficiency virus type I variants (184V) require multiple amino acid changes to become co-resistant to zidovudine in vivo. J Infect Dis 1997; 176: 398-105.
79. Miller V, Phillips A, Rottmann C, et al. Dual resistance to zidovudine (ZDV) and lamivudine (3TC) in patients treated with ZDV/3TC combination therapy: Association with therapy failure. J Infect Dis 1998; 177: 1521-1532.
80. Kemp SD, Shi C, Bloor S, et al. A novel polymorphism at codon 333 of human immunodeficiency virus type I reverse transcriptase can facilitate dual resistance to zidovudine and L-2′, 3′-dideoxy-3′-thiacytidine. J Virol 1998; 72: 5093-5098.
81. Winters MA, Coolley KL, Girard YA, et al.A 6-basepair insert in the reverse transcriptase gene of human immunodeficiency virus type I confers resistance to multiple nucleoside. J Clin Invest 1998; 102: 1769-75.
82. Larder BA, Bloor S, Kemp SD, et al.A family of insertion mutations between codons 67 and 70 of human immunodeficiency virus type I reverse transcriptase confer multinucleoside analog resistance. Antimicrob Agents Chemother 1999; 43: 1961-1967.
83. Sugiura W, Matsuda M, Matsuda Z, et al. Identification of insertion mutations in HIV-I reverse transcriptase causing multiple drug resistance to nucleoside analogue reverse transcriptase inhibitors. J Human Virol 1999; 2: 146-153.
84. Boyer PL, Lisziewicz J, Lori F, et al. Analysis of amino insertion mutations in the fingers subdomain of HIV-I reverse transcriptase. J Mol Biol 1999; 286: 995-1008.
85. Shirasaka T, Kavlick MF, Ueno T, et al. Emergence of human immunodeficiency virus type I variants with resistance to multiple dideoxynucleosides in patients receiving therapy with dideoxynucleosides. Proc Natl Acad Sci USA 1995; 92: 2398-2402.
86. Signoretti C, Romagnoli G, Turriziani O, et al. Induction of the multidrug-transporter P-glycoprotein by 3′ azido-3′ deoxythymidine (AZT) treatment in tumor cell lines. J Exp & Clin Can Res 1997; 16: 29-32.
87. Schuetz JD, Connelly MC, Sun DX, et al. MRP4:A previously unidentified factor in resistance to nucleoside-based antiviral drugs. Nature Medicine 1999; 5: 1048-1051.