A Polymorphism at Position 400 in the Connection Subdomain of HIV-1 Reverse Transcriptase Affects Sensitivity to NNRTIs and RNaseH Activity

PLoS ONE

Volumn 8, Issue 10, 2013, Pages

  Wright, David W ^a   Deuzing, Ilona P ^b   Flandre, Philippe ^c   van den Eede, Peter ^d   Govaert, Micheline ^d   Setiawan, Laurentia ^b,e   Coveney, Peter V ^a   Marcelin, Anne Geneviève ^c   Calvez, Vincent ^c   Boucher, Charles A B ^b   Beerens, Nancy ^b  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b ERASMUS MEDICAL CENTER   (Netherlands)

^c INSERM   (France)

^d JANSSEN RESEARCH FOUNDATION   (Belgium)

^e ACADEMIC MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

ABACAVIR; DIDANOSINE; EFAVIRENZ; EMTRICITABINE; ETRAVIRINE; LAMIVUDINE; NEVIRAPINE; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; RIBONUCLEASE H; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; STAVUDINE; TENOFOVIR; THREONINE; VIRUS RNA; ZIDOVUDINE;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ANTIVIRAL RESISTANCE; ANTIVIRAL SUSCEPTIBILITY; ARTICLE; CONNECTION SUBDOMAIN; CONTROLLED STUDY; DRUG TREATMENT FAILURE; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME CONFORMATION; ENZYME POLYMORPHISM; ENZYME STRUCTURE; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HYDROGEN BOND; MOLECULAR DYNAMICS; NONHUMAN; PROTEIN DOMAIN; REVERSE TRANSCRIPTION; RNA GENE; VIRUS GENOME;

DRUG RESISTANCE, VIRAL; GENOMICS; HIV REVERSE TRANSCRIPTASE; HIV-1; MOLECULAR DYNAMICS SIMULATION; POLYMORPHISM, GENETIC; PROTEIN STRUCTURE, TERTIARY; REVERSE TRANSCRIPTASE INHIBITORS; RIBONUCLEASE H, HUMAN IMMUNODEFICIENCY VIRUS; VIRUS REPLICATION;

EID: 84884824794     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0074078     Document Type: Article

References (76)

1. Sarafianos SG, Marchand B, Das K, Himmel DM, Parniak MA, et al. (2009) Structure and function of HIV-1 reverse transcriptase: molecular mechanisms of polymerization and inhibition. J Mol Biol 385: 693-713.
2. Kohlstaedt LA, Wang J, Friedman JM, Rice PA, Steitz TA, (1992) Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 256: 1783-1790.
3. Painter GR, Almond MR, Mao S, Liotta DC, (2004) Biochemical and mechanistic basis for the activity of nucleoside analogue inhibitors of HIV reverse transcriptase. Curr Top Med Chem 4: 1035-1044.
4. Cihlar T, Ray AS, (2010) Nucleoside and nucleotide HIV reverse transcriptase inhibitors: 25 years after zidovudine. Antiviral Research 85: 39-58.
5. de Béthune M-P, (2010) Non-nucleoside reverse transcriptase inhibitors (NNRTIs), their discovery, development, and use in the treatment of HIV-1 infection: A review of the last 20 years (1989-2009). Antiviral Research 85: 75-90.
6. Sluis-Cremer N, Temiz NA, Bahar I, (2004) Conformational changes in HIV-1 reverse transcriptase induced by nonnucleoside reverse transcriptase inhibitor binding. Curr HIV Res 2: 323-332.
7. De Clercq E, (2004) Antiviral drugs in current clinical use. Journal of Clinical Virology 30: 115-133.
8. Menéndez-Arias L, (2008) Mechanisms of resistance to nucleoside analogue inhibitors of HIV-1 reverse transcriptase. Virus Research 134: 124-146.
9. Selmi B, Deval J, Boretto J, Canard B, (2003) Nucleotide analogue binding, catalysis and primer unblocking in the mechanisms of HIV-1 reverse transcriptase-mediated resistance to nucleoside analogues. Antivir Ther 8: 143-154.
10. Gu Z, Arts EJ, Parniak MA, Wainberg MA, (1995) Mutated K65R recombinant reverse transcriptase of human immunodeficiency virus type 1 shows diminished chain termination in the presence of 2′,3′-dideoxycytidine 5′-triphosphate and other drugs. Proc Natl Acad Sci U S A 92: 2760-2764.
11. Ueno T, Shirasaka T, Mitsuya H, (1995) Enzymatic characterization of human immunodeficiency virus type 1 reverse transcriptase resistant to multiple 2′,3′-dideoxynucleoside 5′-triphosphates. J Biol Chem 270: 23605-23611.
12. Krebs R, Immendorfer U, Thrall SH, Wohrl BM, Goody RS, (1997) Single-step kinetics of HIV-1 reverse transcriptase mutants responsible for virus resistance to nucleoside inhibitors zidovudine and 3-TC. Biochemistry 36: 10292-10300.
13. Goldschmidt V, Marquet R, (2004) Primer unblocking by HIV-1 reverse transcriptase and resistance to nucleoside RT inhibitors (NRTIs). The International Journal of Biochemistry & Cell Biology 36: 1687-1705.
14. Boucher CA, O'Sullivan E, Mulder JW, Ramautarsing C, Kellam P, et al. (1992) Ordered appearance of zidovudine resistance mutations during treatment of 18 human immunodeficiency virus-positive subjects. J Infect Dis 165: 105-110.
15. Menendez-Arias L, Martinez MA, Quinones-Mateu ME, Martinez-Picado J, (2003) Fitness variations and their impact on the evolution of antiretroviral drug resistance. Curr Drug Targets Infect Disord 3: 355-371.
16. Wainberg MA, (2004) The impact of the M184V substitution on drug resistance and viral fitness. Expert Rev Anti Infect Ther 2: 147-151.
17. Boucher CA, Cammack N, Schipper P, Schuurman R, Rouse P, et al. (1993) 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. Antimicrob Agents Chemother 37: 2231-2234.
18. White KL, Margot NA, Wrin T, Petropoulos CJ, Miller MD, et al. (2002) Molecular mechanisms of resistance to human immunodeficiency virus type 1 with reverse transcriptase mutations K65R and K65R+M184V and their effects on enzyme function and viral replication capacity. Antimicrob Agents Chemother 46: 3437-3446.
19. Frankel FA, Invernizzi CF, Oliveira M, Wainberg MA, (2007) Diminished efficiency of HIV-1 reverse transcriptase containing the K65R and M184V drug resistance mutations. AIDS 21: 665-675.
20. Boyer PL, Hughes SH, (1995) Analysis of mutations at position 184 in reverse transcriptase of human immunodeficiency virus type 1. Antimicrob Agents Chemother 39: 1624-1628.
21. Domaoal RA, Demeter LM, (2004) Structural and biochemical effects of human immunodeficiency virus mutants resistant to non-nucleoside reverse transcriptase inhibitors. The International Journal of Biochemistry & Cell Biology 36: 1735-1751.
22. Ren J, Stammers DK, (2008) Structural basis for drug resistance mechanisms for non-nucleoside inhibitors of HIV reverse transcriptase. Virus Research 134: 157-170.
23. Yap SH, Sheen CW, Fahey J, Zanin M, Tyssen D, et al. (2007) N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. PLoS Med 4: e335.
24. Brehm JH, Koontz D, Meteer JD, Pathak V, Sluis-Cremer N, et al. (2007) Selection of mutations in the connection and RNase H domains of human immunodeficiency virus type 1 reverse transcriptase that increase resistance to 3′-azido-3′-dideoxythymidine. J Virol 81: 7852-7859.
25. Nikolenko GN, Delviks-Frankenberry KA, Palmer S, Maldarelli F, Fivash MJ Jr, et al. (2007) Mutations in the connection domain of HIV-1 reverse transcriptase increase 3′-azido-3′-deoxythymidine resistance. Proc Natl Acad Sci U S A 104: 317-322.
26. Ehteshami M, Gotte M, (2008) Effects of mutations in the connection and RNase H domains of HIV-1 reverse transcriptase on drug susceptibility. AIDS Rev 10: 224-235.
27. Menéndez-Arias L, Betancor G, Matamoros T, (2011) HIV-1 reverse transcriptase connection subdomain mutations involved in resistance to approved non-nucleoside inhibitors. Antiviral Research 92: 139-149.
28. Roquebert B, Marcelin AG, (2008) The involvement of HIV-1 RNAse H in resistance to nucleoside analogues. J Antimicrob Chemother 61: 973-975.
29. Santos AF, Lengruber RB, Soares EA, Jere A, Sprinz E, et al. (2008) Conservation patterns of HIV-1 RT connection and RNase H domains: identification of new mutations in NRTI-treated patients. PLoS One 3: e1781.
30. Tanuma J, Hachiya A, Ishigaki K, Gatanaga H, Lien TT, et al. (2010) Impact of CRF01_AE-specific polymorphic mutations G335D and A371V in the connection subdomain of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on susceptibility to nucleoside RT inhibitors. Microbes Infect 12: 1170-1177.
31. Delviks-Frankenberry KA, Nikolenko GN, Maldarelli F, Hase S, Takebe Y, et al. (2009) Subtype-specific differences in the human immunodeficiency virus type 1 reverse transcriptase connection subdomain of CRF01_AE are associated with higher levels of resistance to 3′-azido-3′-deoxythymidine. J Virol 83: 8502-8513.
32. Delviks-Frankenberry KA, Lengruber RB, Santos AF, Silveira JM, Soares MA, et al. (2013) Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Virology 435: 433-441.
33. Wright DW, Hall BA, Kellam P, Coveney PV, (2012) Global Conformational Dynamics of HIV-1 Reverse Transcriptase Bound to Non-Nucleoside Inhibitors. Biology 1: 222-244.
34. Delviks-Frankenberry KA, Nikolenko GN, Pathak VK, (2010) The "Connection". Between HIV Drug Resistance and RNase H. Viruses 2: 1476-1503.
35. Nikolenko GN, Delviks-Frankenberry KA, Pathak VK, (2010) A novel molecular mechanism of dual resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors. J Virol 84: 5238-5249.
36. de Jong MD, Veenstra J, Stilianakis NI, Schuurman R, Lange JM, et al. (1996) 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 1 RNA load suppression by zidovudine. Proc Natl Acad Sci U S A 93: 5501-5506.
37. Roquebert B, Wirden M, Simon A, Deval J, Katlama C, et al. (2007) Relationship between mutations in HIV-1 RNase H domain and nucleoside reverse transcriptase inhibitors resistance mutations in naive and pre-treated HIV infected patients. J Med Virol 79: 207-211.
38. Benjamini Y, Drai D, Elmer G, Kafkafi N, Golani I, (2001) Controlling the false discovery rate in behavior genetics research. Behav Brain Res 125: 279-284.
39. Adachi A, Gendelman HE, Koenig S, Folks T, Willey R, et al. (1986) Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J Virol 59: 284-291.
40. Buxton P, Tachedjian G, Mak J, (2005) Analysis of the contribution of reverse transcriptase and integrase proteins to retroviral RNA dimer conformation. J Virol 79: 6338-6348.
41. Pattery T, Verlinden Y, De Wolf H, Nauwelaers D, Van Baelen K, et al. (2012) Development and performance of conventional HIV-1 phenotyping (Antivirogram(R)) and genotype-based calculated phenotyping assay (virco(R)TYPE HIV-1) on protease and reverse transcriptase genes to evaluate drug resistance. Intervirology 55: 138-146.
42. Humphrey W, Dalke A, Schulten K (1996) VMD: visual molecular dynamics. J Mol Graph 14: 33-38, 27-38.
43. Guex N, Peitsch MC, (1997) SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 18: 2714-2723.
44. Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML, (1983) Comparison of simple potential functions for simulating liquid water. The Journal of Chemical Physics 79: 926-935.
45. Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA, (2004) Development and testing of a general amber force field. J Comput Chem 25: 1157-1174.
46. Duan Y, Wu C, Chowdhury S, Lee MC, Xiong G, et al. (2003) A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations. J Comput Chem 24: 1999-2012.
47. Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E, et al. (2005) Scalable molecular dynamics with NAMD. J Comput Chem 26: 1781-1802.
48. Case DA, Cheatham TE 3rd, Darden T, Gohlke H, Luo R, et al. (2005) The Amber biomolecular simulation programs. J Comput Chem 26: 1668-1688.
49. Lu XJ, Olson WK, (2008) 3DNA: a versatile, integrated software system for the analysis, rebuilding and visualization of three-dimensional nucleic-acid structures. Nat Protoc 3: 1213-1227.
50. Lu XJ, Olson WK, (2003) 3DNA: a software package for the analysis, rebuilding and visualization of three-dimensional nucleic acid structures. Nucleic Acids Res 31: 5108-5121.
51. Johnson VA, Calvez V, Gunthard HF, Paredes R, Pillay D, et al. (2011) 2011 update of the drug resistance mutations in HIV-1. Top Antivir Med 19: 156-164.
52. Larder BA, Darby G, Richman DD, (1989) HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. Science 243: 1731-1734.
53. Ceccherini-Silberstein F, Svicher V, Sing T, Artese A, Santoro MM, et al. (2007) Characterization and structural analysis of novel mutations in human immunodeficiency virus type 1 reverse transcriptase involved in the regulation of resistance to nonnucleoside inhibitors. J Virol 81: 11507-11519.
54. Gonzales MJ, Wu TD, Taylor J, Belitskaya I, Kantor R, et al. (2003) Extended spectrum of HIV-1 reverse transcriptase mutations in patients receiving multiple nucleoside analog inhibitors. AIDS 17: 791-799.
55. Marcelin AG, Flandre P, Furco A, Wirden M, Molina JM, et al. (2006) Impact of HIV-1 reverse transcriptase polymorphism at codons 211 and 228 on virological response to didanosine. Antivir Ther 11: 693-699.
56. Sarafianos SG, Das K, Tantillo C, Clark AD Jr, Ding J, et al. (2001) Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA:DNA. EMBO J 20: 1449-1461.
57. Dash C, Scarth BJ, Badorrek C, Gotte M, Le Grice SF, (2008) Examining the ribonuclease H primer grip of HIV-1 reverse transcriptase by charge neutralization of RNA/DNA hybrids. Nucleic Acids Res 36: 6363-6371.
58. Turner KB, Yi-Brunozzi HY, Brinson RG, Marino JP, Fabris D, et al. (2009) SHAMS: combining chemical modification of RNA with mass spectrometry to examine polypurine tract-containing RNA/DNA hybrids. RNA 15: 1605-1613.
59. Nowotny M, Gaidamakov SA, Crouch RJ, Yang W, (2005) Crystal structures of RNase H bound to an RNA/DNA hybrid: substrate specificity and metal-dependent catalysis. Cell 121: 1005-1016.
60. Noy A, Perez A, Marquez M, Luque FJ, Orozco M, (2005) Structure, recognition properties, and flexibility of the DNA.RNA hybrid. J Am Chem Soc 127: 4910-4920.
61. van Westen GJ, Hendriks A, Wegner JK, Ijzerman AP, van Vlijmen HW, et al. (2013) Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. PLoS Comput Biol 9: e1002899.
62. Harrigan PR, Salim M, Stammers DK, Wynhoven B, Brumme ZL, et al. (2002) A mutation in the 3′ region of the human immunodeficiency virus type 1 reverse transcriptase (Y318F) associated with nonnucleoside reverse transcriptase inhibitor resistance. J Virol 76: 6836-6840.
63. Pelemans H, Esnouf RM, Jonckheere H, De Clercq E, Balzarini J, (1998) Mutational analysis of Tyr-318 within the non-nucleoside reverse transcriptase inhibitor binding pocket of human immunodeficiency virus type I reverse transcriptase. J Biol Chem 273: 34234-34239.
64. Hachiya A, Kodama EN, Sarafianos SG, Schuckmann MM, Sakagami Y, et al. (2008) Amino acid mutation N348I in the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase confers multiclass resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors. J Virol 82: 3261-3270.
65. Sluis-Cremer N, Moore K, Radzio J, Sonza S, Tachedjian G, (2010) N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. AIDS 24: 317-319.
66. Schuckmann MM, Marchand B, Hachiya A, Kodama EN, Kirby KA, et al. (2010) The N348I mutation at the connection subdomain of HIV-1 reverse transcriptase decreases binding to nevirapine. J Biol Chem 285: 38700-38709.
67. Biondi MJ, Beilhartz GL, McCormick S, Gotte M, (2010) N348I in HIV-1 reverse transcriptase can counteract the nevirapine-mediated bias toward RNase H cleavage during plus-strand initiation. J Biol Chem 285: 26966-26975.
68. Ehteshami M, Beilhartz GL, Scarth BJ, Tchesnokov EP, McCormick S, et al. (2008) Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3′-azido-3′-deoxythymidine through both RNase H-dependent and-independent mechanisms. J Biol Chem 283: 22222-22232.
69. Nikolenko GN, Palmer S, Maldarelli F, Mellors JW, Coffin JM, et al. (2005) Mechanism for nucleoside analog-mediated abrogation of HIV-1 replication: balance between RNase H activity and nucleotide excision. Proc Natl Acad Sci U S A 102: 2093-2098.
70. Das K, Clark AD Jr, Lewi PJ, Heeres J, De Jonge MR, et al. (2004) Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants. J Med Chem 47: 2550-2560.
71. Braz VA, Holladay LA, Barkley MD, (2010) Efavirenz binding to HIV-1 reverse transcriptase monomers and dimers. Biochemistry 49: 601-610.
72. Xia Q, Radzio J, Anderson KS, Sluis-Cremer N, (2007) Probing nonnucleoside inhibitor-induced active-site distortion in HIV-1 reverse transcriptase by transient kinetic analyses. Protein Sci 16: 1728-1737.
73. von Wyl V, Ehteshami M, Symons J, Burgisser P, Nijhuis M, et al. (2010) Epidemiological and biological evidence for a compensatory effect of connection domain mutation N348I on M184V in HIV-1 reverse transcriptase. J Infect Dis 201: 1054-1062.
74. Larder BA, Kemp SD, Harrigan PR, (1995) Potential mechanism for sustained antiretroviral efficacy of AZT-3TC combination therapy. Science 269: 696-699.
75. Kemp SD, Shi C, Bloor S, Harrigan PR, Mellors JW, et al. (1998) A novel polymorphism at codon 333 of human immunodeficiency virus type 1 reverse transcriptase can facilitate dual resistance to zidovudine and L-2′,3′-dideoxy-3′-thiacytidine. J Virol 72: 5093-5098.
76. Radzio J, Yap SH, Tachedjian G, Sluis-Cremer N, (2010) N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. AIDS 24: 659-667.