Characterization and structural analysis of novel mutations in human immunodeficiency virus type 1 reverse transcriptase involved in the regulation of resistance to nonnucleoside inhibitors

Journal of Virology

Volumn 81, Issue 20, 2007, Pages 11507-11519

  Ceccherini Silberstein, Francesca ^a   Svicher, Valentina ^a   Sing, Tobias ^b   Artese, Anna ^c,d   Santoro, Maria Mercedes ^a   Forbici, Federica ^e   Bertoli, Ada ^a   Alcaro, Stefano ^c,d   Palamara, Guido ^f   Monforte, Antonella D'Arminio ^g   Balzarini, Jan ^h   Antinori, Andrea ^e   Lengauer, Thomas ^b   Perno, Carlo Federico ^a,e  

^a UNIVERSITY OF ROME TOR VERGATA   (Italy)

^b MAX PLANCK INSTITUTE FOR INFORMATICS   (Germany)

^c UNIVERSITY MAGNA GRAECIA OF CATANZARO   (Italy)

^d INFN LABORATORI NAZIONALI DI FRASCATI   (Italy)

^e NATIONAL INSTITUTE FOR INFECTIOUS DISEASES L SPALLANZANI   (Italy)

^f San Gallicane Hospital   (Italy)

^g UNIVERSITY OF MILAN   (Italy)

^h REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; EFAVIRENZ; NEVIRAPINE; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; THYMIDINE DERIVATIVE; ZIDOVUDINE;

ARTICLE; CONTROLLED STUDY; DRUG BINDING SITE; DRUG TREATMENT FAILURE; GENE MUTATION; GENE SEQUENCE; GENETIC POLYMORPHISM; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYDROGEN BOND; MAJOR CLINICAL STUDY; MOLECULAR DYNAMICS; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; SIMULATION; STRUCTURAL GENE; TREATMENT RESPONSE; VIRUS RESISTANCE;

ANTI-HIV AGENTS; BASE SEQUENCE; DRUG RESISTANCE, VIRAL; HIV REVERSE TRANSCRIPTASE; HUMANS; MOLECULAR SEQUENCE DATA; MUTATION, MISSENSE; REVERSE TRANSCRIPTASE INHIBITORS;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 35148845529     PISSN: 0022538X     EISSN: None     Source Type: Journal    
DOI: 10.1128/JVI.00303-07     Document Type: Article

References (53)

1. Bacheler, L. T., E. D. Anton, P. Kudish, D. Baker, J. Bunville, K. Krakowski, L. Bolling, M. Aujay, X. V. Wang, D. Ellis, M. F. Becker, A. L. Lasut, H. J. George, D. R. Spalding, G. Hollis, and K. Abremski. 2000. Human immunodeficiency virus type 1 mutations selected in patients failing efavirenz combination therapy. Antimicrob. Agents Chemother. 44:2475-2484.
2. Balzarini, J. 2004. Current status of the non-nucleoside reverse transcriptase inhibitors of human immunodeficiency virus type 1. Curr. Top. Med. Chem. 4:921-944.
3. Beerenwinkel, N., M. Daumer, M. Oette, K. Korn, D. Hoffmann, R. Kaiser, T. Lengauer, J. Selbig, and H. Walter. 2003. Geno2pheno: estimating phenotypic drug resistance from HIV-1 genotypes. Nucleic Acids Res. 31:3850-3855.
4. Benjamin!, Y., and Y. Hochberg. 1995. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B 57:289-300.
5. Berendsen, H., J. Postma, W. Van Gunsteren, A. Di Nola, and J. Haak. 1984. Molecular dynamics with coupling to an external bath. J. Chem. Phys. 81:3584-3590.
6. Berendsen, H., D. Van der Spoel, and R. Van Drunen. 1995. GROMACS: a message-passing parallel molecular dynamics implementation. Comp. Phys. Comm. 91:43-56.
7. Boyer, P. L., H. Q. Gao, and S. H. Hughes. 1998. A mutation at position 190 of human immunodeficiency virus type 1 reverse transcriptase interacts with mutations at positions 74 and 75 via the template primer. Antimicrob. Agents Chemother. 42:447-452.
8. Brown, A. J., H. M. Precious, J. M. Whitcomb, J. K. Wong, M. Quigg, W. Huang, E. S. Daar, R. T. D'Aquila, P. H. Keiser, E. Connick, N. S. Hellmann, C. J. Petropoulos, D. D. Richman, and S. Little. 2000. Reduced susceptibility of human immunodeficiency virus type 1 (HIV-1) from patients with primary HIV infection to nonnucleoside reverse transcriptase inhibitors is associated with variation at novel amino acid sites. J. Virol. 74:10269-10273.
9. Camacho, R., K. Theys, A. Abecasis, K. Deforche, A. P. Carvalho, J. Cabanas, P. Gomes, and A. M. Vandamme. 2006. XV Int. HIV Drug Resist. Workshop Basic Princ. Clin. Implications, abstr. 148.
10. Ceccherini-Silberstein, F., F. Erba, F. Gago, A. Bertoli, F. Forbici, M. C. Bellocchi, C. Gori, R. D'Arrigo, L. Marcon, C. Balotta, A. Antinori, A. D'Arminio Monforte, and C. F. Perno. 2004. Identification of the minimal conserved structure of HIV-1 protease in the presence or absence of drug pressure. AIDS 18:11-19.
11. Ceccherini-Silberstein, F., F. Gago, M. Santoro, C. Gori, V. Svicher, F. Rodríguez-Barrios, R. D'Arrigo, M. Ciccozzi, A. Bertoli, A. D'Arminio Monforte, J. Balzarini, A. Antinori, and C. F. Perno. 2005. High sequence conservation of human immunodeficiency virus type 1 reverse transcriptase under drug pressure despite the continuous appearance of mutations. J. Virol. 79:10718-10729.
12. Chen, L., A. Perlina, and C. J. Lee. 2004. Positive selection detection in 40,000 human immunodeficiency virus (HIV) type 1 sequences automatically identifies drug resistance and positive fitness mutations in HIV protease and reverse transcriptase. J. Virol. 78:3722-3732.
13. Clark, S. A., N. S. Shulman, R. J. Bosch, and J. W. Mellors. 2006. Reverse transcriptase mutations 1181, 208Y, and 215Y cause HIV-1 hypersusceptibility to non-nucleoside reverse transcriptase inhibitors. AIDS 20:981-984.
14. Clavel, F., and A. J. Hance. 2004. HIV drug resistance. N. Engl. J. Med. 350:1023-1035.
15. Darden, T., D. York, and L. Pedersen. 1993. Particle mesh Ewald. J. Chem. Phys. 98:10089-10092.
16. De Clercq, E. 2004. Antivirale and antiviral strategies. Nat. Rev. Microbiol. 2:704-720.
17. De Groot, A. S., B. M. Jesdale, E. Szu, J. R. Schafer, R. M. Chicz, and G. Deocampo. 1997. An interactive Web site providing major histocompatibility ligand predictions: application to HIV research. AIDS Res. Hum. Retrovir. 13:529-531.
18. Geitmann, M., T. Unge, and U. H. Danielson. 2006. Interaction kinetic characterization of HIV-1 reverse transcriptase non-nucleoside inhibitor resistance. J. Med. Chem. 49:2375-2387.
19. Gonzales, M. J., T. D. Wu, J. Taylor, I. Belitskaya, R. Kantor, D. Israelski, S. Chou, A. R. Zolopa, W. J. Fessel, and R. W. Shafer. 2003. Extended spectrum of HIV-1 reverse transcriptase mutations in patients receiving multiple nucleoside analog inhibitors. AIDS 17:791-799.
20. Götte, M., X. Li, and M. A. Wainberg. 1999. HIV-1 reverse transcription: a brief overview focused on structure-function relationships among molecules involved in initiation of the reaction. Arch. Biochem. Biophys. 365:199-210.
21. Hess, B., H. Bekker, H. Berendsen, and J. Fraaije. 1997. A linear constraint solver for molecular simulations. J. Comp. Chem. 18:1463-1472.
22. Hope, A. C. 1968. A simplified Monte Carlo significance test procedure. J. R. Stat. Soc. Ser. B 30:582-598.
23. Hsiou, Y., J. Ding, K. Das, A. D. Clark, Jr., S. H. Hughes, and E. Arnold. 1996. Structure of unliganded HIV-1 reverse transcriptase at 2.7 A resolution: implications of conformational changes for polymerization and inhibition mechanisms. Structure 4:853-860.
24. Hsiou, Y., J. Ding, K. Das, A. D. Clark, P. L. Boyer, P. Lewi, P. A. Janssen, J. P. Kleim, M. Rosner, S. H. Hughes, and E. Arnold. 2001. The Lys103Asn mutation of HIV- RT: a novel mechanism of drug resistance. J. Mol. Biol. 309:437-445.
25. Johnson, V. A., F. Brun-Vezinet, B. Clotet, D. R. Kuritzkes, D. Pillay, J. M. Schapiro, and A. D. D. Richman. 2006. Update of the drug resistance mutations in HIV-1: fall 2006. Top. HIV Med. 14:125-130.
26. Kleim, J. P., M. Rosner, I. Winkler, A. Paessens, R. Kirsh, Y. Hsiou, E. Arnold, and G. Reiss. 1996. Selective pressure of a quinoxaline nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on HIV-1 replication results in the emergence of nucleoside RT-inhibitor-specific (RT Leu-74→Val or Ile and Val-75→Leu or Ile) HIV-1 mutants. Proc. Natl. Acad. Sci. USA 93:34-38.
27. Koval, C. E., C. Dykes, J. Wang, and L. M. Demeter. 2006. Relative replication fitness of efavirenz-resistant mutants of HIV-1: correlation with frequency during clinical therapy and evidence of compensation for the reduced fitness of K103N + L1001 by the nucleoside resistance mutation L74V. Virology 353:184-192.
28. Larder, B. A. 1994. Interactions between drug resistance mutations in human immunodeficiency virus type 1 reverse transcriptase. J. Gen. Virol. 75:951-957.
29. Lebowitz, J., S. Kar, E. Braswell, S. McPherson, and D. L. Richard. 1994. Human immunodeficiency virus-1 reverse transcriptase heterodimer stability. Protein Sci. 3:1374-1382.
30. Moore, C. B., M. John, I. R. James, F. T. Christiansen, C. S. Witt, and S. A. Mahal. 2002. Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level. Science 296:1439-1443.
31. Oostenbrink, C., A. Villa, A. Marck, and W. Van Gunsteren. 2004. A biomolecular force field based on the free enthalpy of hydration and solvation: the GROMOS force-field parameter sets 53A5 and 53A6. J. Comp. Chem. 25:1656.
32. Parniak, M. A., and N. Sluis-Cremer. 2000. Inhibitors of HIV-1 reverse transcriptase. Adv. Pharmacol. 49:67-109.
33. Perno, C. F., A. Cozzi-Lepri, C. Balotta, F. Forbici, M. Violin, A. Bertoli, G. Facchi, P. Pezzati, G. Cadeo, G. Tositti, S. Pasquinucci, S. Pauluzzi, A. Scalzini, B. Salassa, A. Vincent!, A. N. Phillips, F. Dianzani, A. Apice, G. Angarano, L. Monno, G. Ippolito, M. Moroni, and A. D'Arminio Manforte. 2001. Secondary mutations in the protease region of human immunodeficiency virus and virological failure in drug-naïve patients treated with protease inhibitor based therapy. J. Infect. Dis. 184:983-991.
34. Ren, J., C. Nichols, L. Bird, P. Chamberlein, K. Weaver, S. Short, D. I. Stuart, and D. K. Stammers. 2001. Structural mechanisms of drug resistance for mutations at codons 181 and 188 in HIV-1 reverse transcriptase and the improved resilience of second generation non-nucleoside inhibitors. J. Mol. Biol. 312:795-802.
35. Rhee, S. Y., W. J. Fessel, A. R. Zolopa, L. Hurley, T. Liu, J. Taylor, D. P. Nugyen, S. Slome, D. Klein, M. Horberg, J. Flamm, S. Follansbee, J. M. Schapiro, and R. W. Shafer. 2005. HIV-1 protease and reverse-transcriptase mutations: correlations with antiretroviral therapy in subtype B isolates and implications for drug-resistance surveillance. J. Infect. Dis. 192:456-465.
36. Rhee, S. Y., J. Taylor, G. Wadhera, A. Ben-Hur, D. L. Brutlag, and R. W. Shafer. 2006. Genotypic predictors of human immunodeficiency virus type 1 drug resistance. Proc. Natl. Acad. Sci. USA 103:17355-17360.
37. Saracino, A., L. Monno, L. Scudeller, D. C. Cibelli, A. Tartaglia, G. Punzi, C. Torti, S. Lo Caputo, S. Mazzotta, G. Scotto, G. Carosi, and G. Angarano. 2006. Impact of unreported HIV-1 reverse transcriptase mutations on phenotypic resistance to nucleoside and non-nucleoside inhibitors. J. Med. Virol. 78:9-17.
38. Schinazi, R. F., B. A. Larder, and J. Mellors. 2000. Mutations in retroviral genes associated to drug resistance: update 2000-2001. Int. Antivir. News 8:65-91.
39. Selmi, B., J. Deval, K. Alvarez, J. Boretto, S. Sarfati, C. Guerreiro, and B. Canard. 2003. The Y181C substitution in 3′-azido-3′- deoxythymidine-resistant human immunodeficiency virus, type 1, reverse transcriptase suppresses the ATP-mediated repair of the 3′-azido-3′- deoxythymidine 5′-monophosphate-terminated primer. J. Biol. Chem. 278:40464-40472.
40. Shafer, R. W. 2002. Genotypic testing for human immunodeficiency virus type 1 drug resistance. Clin. Microbiol. Rev. 15:247-277.
41. Shulman, N. S., R. J. Bosch, J. W. Mellors, M. A. Albrecht, and D. A. Katzenstein. 2004. Genetic correlates of efavirenz hypersusceptibility. AIDS 18:1781-1785.
42. Shulman, N. S., J. Delgado, R. J. Bosch, M. A. Winters, E. Johnston, R. W. Shafer, D. A. Katzenstein, and T. C. Merigan. 2005. Nonnucleoside reverse transcriptase inhibitor phenotypic hypersusceptibility can be demonstrated in different assays. J. Acquir. Immune Defic. Syndr. 39:78-81.
43. Sing, T., V. Svicher, N. Beerenwinkel, F. Ceccherini-Silberstein, M. Daumer, R. Kaiser, H. Walter, K. Korn, D. Hoffmann, and M. Oette. 2005. Characterization of novel HIV drug resistance mutations using clustering, multidimensional scaling and SVM-based feature ranking, p. 285-296. In A. Jorge, L. Torgo, P. Brazdil, R. Camacho, and J. Gama (ed.), Knowledge discovery in databases: PKDD. Springer, New York, NY.
44. Svicher, V., T. Sing, M. M. Santoro, F. Forbid, F. Rodríguez-Barrios, A. Bertoli, N. Beerenwinkel, M. C. Bellocchi, F. Gago, A. D'Arminio Manforte, and C. F. Perno. 2006. Involvement of novel human immunodeficiency virus type 1 reverse transcriptase mutations in the regulation of resistance to nucleoside inhibitors. J. Virol. 80:7186-7198.
45. Telesnitsky, A., and S. P. Goff. 1997. Reverse transcriptase and the generation of retroviral DNA, p. 121-160. In J. M. Coffin, S. H. Hughes, and H. E. Varmus (ed.). Retroviruses. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
46. Tozzi, V., M. Zaccarelli, P. Narciso, M. P. Trotta, F. Ceccherini-Silberstein, P. De Longis, G. D'Offizi, F. Forbici, R. D'Arrigo, E. Boumis, and C. F. Perno. 2004. Mutations in HIV-1 reverse transcriptase potentially associated with hypersusceptibility to nonnucleoside reverse-transcriptase inhibitors: effect on response to efavirenz-based therapy in an urban observational cohort. J. Infect. Dis. 189:1688-1695.
47. Van Laethem, K., M. Witvrouw, C. Pannecouque, B. Van Remoortel, J. C. Schmit, R. Esnouf, J. P. Kleim, J. Balzarini, J. Desmyter, E. De Clercq, and A. M. Vandamme. 2001. Mutations in the non-nucleoside binding-pocket interfere with the multi-nucleoside resistance phenotype. AIDS 15:553-561.
48. Vavro, C., A. Florence, D. Irlbeck, B. Wine, and M. St. Clair. 2004. Abstr. 11th Conf. Retrovir. Opport. Infect., abstr. 658.
49. Vingerhoets, J., H. Azijn, E. Fransen, I. De Baere, L. Smeulders, D. Jochmans, K. Andries, R. Pauwels, and M. P. De Bethune. 2005. TMC125 displays a high genetic barrier to the development of resistance: evidence from in vitro selection experiments. J. Virol. 79:12773-12782.
50. Wainberg, M. A. 2004. HIV-1 subtype distribution and the problem of drug resistance. AIDS 18:63-68.
51. Wallace, A. C., R. A. Laskowski, and J. Thornton. 1995. LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng. 8:127-134.
52. Walter, H., B. Schmidt, K. Korn, A. M. Vandamme, T. Harrer, and K. Uberla. 1999. Rapid, phenotypic HIV-1 drug sensitivity assay for protease and reverse transcriptase inhibitors. J. Clin. Virol. 13:71-80.
53. Wu, T. D., C. A. Schiffer, M. J. Gonzales, J. Taylor, R. Kantor, S. Chou, D. Israelski, A. R. Zolopa, W. J. Fessel, and R. W. Shafer. 2003. Mutation patterns and structural correlates in human immunodeficiency virus type 1 protease following different protease inhibitor treatments. J. Virol. 77:4836-4847.