The M230L nonnucleoside reverse transcriptase inhibitor resistance mutation in HIV-1 reverse transcriptase impairs enzymatic function and viral replicative capacity

Antimicrobial Agents and Chemotherapy

Volumn 54, Issue 6, 2010, Pages 2401-2408

  Xu, Hong Tao ^a   Quan, Yudong ^a   Schader, Susan M ^a,b   Oliveira, Maureen ^a   Bar Magen, Tamara ^a   Wainberg, Mark A ^a,b  

^a MCGILL UNIVERSITY   (Canada)

^b MCGILL UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

EFAVIRENZ; ETRAVIRINE; NEVIRAPINE; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; RNA DIRECTED DNA POLYMERASE;

ARTICLE; CONTROLLED STUDY; DNA SYNTHESIS; ENZYME INHIBITION; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; PRIORITY JOURNAL; VIRUS MUTATION; VIRUS RECOMBINANT; VIRUS REPLICATION; VIRUS RESISTANCE;

ANTI-HIV AGENTS; BASE SEQUENCE; CELL LINE; DNA, VIRAL; DRUG RESISTANCE, VIRAL; HIV REVERSE TRANSCRIPTASE; HIV-1; HUMANS; MUTATION; RECOMBINANT PROTEINS; REVERSE TRANSCRIPTASE INHIBITORS; VIRUS REPLICATION;

EID: 77952606637     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.01795-09     Document Type: Article

References (48)

1. Adachi, A., H. E. Gendelman, S. Koenig, T. Folks, R. Willey, A. Rabson, and M. A. Martin. 1986. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J. Virol. 59:284-291.
2. Antela, A., J. Casado, A. Moreno, F. Dronda, M. Perez-Elias, and S. Moreno. 2001. Clinical relevance of the m230l mutation in the reverse transcriptase gene in patients rescued with a regimen including NNRTIs, abstr. 571. 1st IAS Conf. HIV Pathog.
3. Arion, D., N. Kaushik, S. McCormick, G. Borkow, and M. A. Parniak. 1998. 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. Biochemistry 37: 15908-15917.
4. Arts, E. J., X. Li, Z. Gu, L. Kleiman, M. A. Parniak, and M. A. Wainberg. 1994. Comparison of deoxyoligonucleotide and tRNA(Lys-3) as primers in an endogenous human immunodeficiency virus-1 in vitro reverse transcription/ template-switching reaction. J. Biol. Chem. 269:14672-14680.
5. Azijn, H., I. Tirry, J. Vingerhoets, M. P. de Bethune, G. Kraus, K. Boven, D. Jochmans, E. Van Craenenbroeck, G. Picchio, and L. T. Rimsky. 2010. TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1. Antimicrob. Agents Chemother. 54:718-727.
6. Back, N. K., M. Nijhuis, W. Keulen, C. A. Boucher, B. O. Oude Essink, A. B. van Kuilenburg, A. H. van Gennip, and B. Berkhout. 1996. Reduced replication of 3TC-resistant HIV-1 variants in primary cells due to a processivity defect of the reverse transcriptase enzyme. EMBO J. 15:4040-4049.
7. Boyer, P. L., and S. H. Hughes. 1995. Analysis of mutations at position 184 in reverse transcriptase of human immunodeficiency virus type 1. Antimicrob. Agents Chemother. 39:1624-1628.
8. Caliendo, A. M., A. Savara, D. An, K. DeVore, J. C. Kaplan, and R. T. D'Aquila. 1996. Effects of zidovudine-selected human immunodeficiency virus type 1 reverse transcriptase amino acid substitutions on processive DNA synthesis and viral replication. J. Virol. 70:2146-2153.
9. Cases-Gonzalez, C. E., and L. Menendez-Arias. 2004. Increased G→A transition frequencies displayed by primer grip mutants of human immunodeficiency virus type 1 reverse transcriptase. J. Virol. 78:1012-1019.
10. Deeks, S. G. 2001. International perspectives on antiretroviral resistance. Nonnucleoside reverse transcriptase inhibitor resistance. J. Acquir. Immune Defic. Syndr. 26(Suppl. 1):S25-S33.
11. Diallo, K., B. Marchand, X. Wei, L. Cellai, M. Gotte, and M. A. Wainberg. 2003. Diminished RNA primer usage associated with the L74V and M184V mutations in the reverse transcriptase of human immunodeficiency virus type 1 provides a possible mechanism for diminished viral replication capacity. J. Virol. 77:8621-8632.
12. Dykes, C., and L. M. Demeter. 2007. Clinical significance of human immunodeficiency virus type 1 replication fitness. Clin. Microbiol. Rev. 20:550-578.
13. Frankel, F. A., C. F. Invernizzi, M. Oliveira, and M. A. Wainberg. 2007. Diminished efficiency of HIV-1 reverse transcriptase containing the K65R and M184V drug resistance mutations. AIDS 21:665-675. (Pubitemid 46568623)
14. Freed, E. O., and M. A. Martin. 1994. Evidence for a functional interaction between the V1/V2 and C4 domains of human immunodeficiency virus type 1 envelope glycoprotein gp120. J. Virol. 68:2503-2512. (Pubitemid 24091930)
15. Gerondelis, P., R. H. Archer, C. Palaniappan, R. C. Reichman, P. J. Fay, R. A. Bambara, and L. M. Demeter. 1999. The P236L delavirdine-resistant human immunodeficiency virus type 1 mutant is replication defective and demonstrates alterations in both RNA 5′-end- and DNA 3′-end-directed RNase H activities. J. Virol. 73:5803-5813.
16. Ghosh, M., P. S. Jacques, D. W. Rodgers, M. Ottman, J. L. Darlix, and S. F. Le Grice. 1996. Alterations to the primer grip of p66 HIV-1 reverse transcriptase and their consequences for template-primer utilization. Biochemistry 35:8553-8562.
17. Goff, S., P. Traktman, and D. Baltimore. 1981. Isolation and properties of Moloney murine leukemia virus mutants: use of a rapid assay for release of virion reverse transcriptase. J. Virol. 38:239-248.
18. Gopalakrishnan, V., J. A. Peliska, and S. J. Benkovic. 1992. Human immunodeficiency virus type 1 reverse transcriptase: spatial and temporal relationship between the polymerase and RNase H activities. Proc. Natl. Acad. Sci. U. S. A. 89:10763-10767.
19. Gutierrez-Rivas, M., and L. Menendez-Arias. 2001. A mutation in the primer grip region of HIV-1 reverse transcriptase that confers reduced fidelity of DNA synthesis. Nucleic Acids Res. 29:4963-4972. (Pubitemid 34065411)
20. Hirschel, B., and P. Francioli. 1998. Progress and problems in the fight against AIDS. N. Engl. J. Med. 338:906-908.
21. Huang, W., A. Gamarnik, K. Limoli, C. J. Petropoulos, and J. M. Whitcomb. 2003. Amino acid substitutions at position 190 of human immunodeficiency virus type 1 reverse transcriptase increase susceptibility to delavirdine and impair virus replication. J. Virol. 77:1512-1523. (Pubitemid 36055571)
22. Huang, W., N. T. Parkin, Y. S. Lie, T. Wrin, R. Haubrich, S. Deeks, N. Hellman, C. J. Petropoulos, and J. M. Whitcomb. 2000. A novel HIV-1 RT mutation (M230L) confers NNRTI resistance and dose-dependent stimulation of replication. Antivir. Ther. 5(Suppl. 3):24-25.
23. Huang, W., T. Wrin, A. Gamarnik, J. Beauchaine, J. M. Whitcomb, and C. J. Petropoulos. 2002. Reverse transcriptase mutations that confer nonnucleoside reverse transcriptase inhibitor resistance may also impair replication capacity. Antivir. Ther. 7(Suppl. 1):S60.
24. Isaka, Y., S. Miki, S. Kawauchi, A. Suyama, H. Sugimoto, A. Adachi, T. Miura, M. Hayami, O. Yoshie, T. Fujiwara, and A. Sato. 2001. A single amino acid change at Leu-188 in the reverse transcriptase of HIV-2 and SIV renders them sensitive to non-nucleoside reverse transcriptase inhibitors. Arch. Virol. 146:743-755.
25. Jacques, P. S., B. M. Wohrl, M. Ottmann, J. L. Darlix, and S. F. Le Grice. 1994. Mutating the "primer grip" of p66 HIV-1 reverse transcriptase implicates tryptophan-229 in template-primer utilization. J. Biol. Chem. 269: 26472-26478.
26. Johnson, L. B., and L. D. Saravolatz. 2009. Etravirine, a next-generation nonnucleoside reverse-transcriptase inhibitor. Clin. Infect. Dis. 48:1123-1128.
27. Le Grice, S. F., and F. Gruninger-Leitch. 1990. Rapid purification of homodimer and heterodimer HIV-1 reverse transcriptase by metal chelate affinity chromatography. Eur. J. Biochem. 187:307-314.
28. Llibre, J. M., J. R. Santos, T. Puig, J. Molto, L. Ruiz, R. Paredes, and B. Clotet. 2008. Prevalence of etravirine-associated mutations in clinical samples with resistance to nevirapine and efavirenz. J. Antimicrob. Chemother. 62:909-913.
29. Munshi, V., M. Lu, P. Felock, R. J. Barnard, D. J. Hazuda, M. D. Miller, and M. T. Lai. 2008. Monitoring the development of non-nucleoside reverse transcriptase inhibitor-associated resistant HIV-1 using an electrochemiluminescence-based reverse transcriptase polymerase assay. Anal. Biochem. 374:121-132.
30. Olmsted, R. A., D. E. Slade, L. A. Kopta, S. M. Poppe, T. J. Poel, S. W. Newport, K. B. Rank, C. Biles, R. A. Morge, T. J. Dueweke, Y. Yagi, D. L. Romero, R. C. Thomas, S. K. Sharma, and W. G. Tarpley. 1996. (Alkylamino) piperidine bis(heteroaryl)piperizine analogs are potent, broad-spectrum nonnucleoside reverse transcriptase inhibitors of drug-resistant isolates of human immunodeficiency virus type 1 (HIV-1) and select for drug-resistant variants of HIV-1IIIB with reduced replication phenotypes. J. Virol. 70: 3698-3705.
31. Palaniappan, C., M. Wisniewski, P. S. Jacques, S. F. Le Grice, P. J. Fay, and R. A. Bambara. 1997. Mutations within the primer grip region of HIV-1 reverse transcriptase result in loss of RNase H function. J. Biol. Chem. 272:11157-11164.
32. Powell, M. D., M. Ghosh, P. S. Jacques, K. J. Howard, S. F. Le Grice, and J. G. Levin. 1997. Alanine-scanning mutations in the "primer grip" of p66 HIV-1 reverse transcriptase result in selective loss of RNA priming activity. J. Biol. Chem. 272:13262-13269.
33. Schiller, D. S., and M. Youssef-Bessler. 2009. Etravirine: a second-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) active against NNRTI-resistant strains of HIV. Clin. Ther. 31:692-704.
34. Slade, D. E., T. J. Dueweke, S. M. Poppe, S. M. Swaney, S. M. Wisniewski, V. Sharova, M. Stevenson, and W. G. Tarpley. 1995. HIV-1 acquires resistance to AZT and delavirdine in vitro by multiple RT substitutions, abstr. P-89. Abstr. 2nd Natl. Conf. Hum. Retrovir. Relat. Infect.
35. Smerdon, S. J., J. Jager, J. Wang, L. A. Kohlstaedt, A. J. Chirino, J. M. Friedman, P. A. Rice, and T. A. Steitz. 1994. Structure of the binding site for nonnucleoside inhibitors of the reverse transcriptase of human immunodeficiency virus type 1. Proc. Natl. Acad. Sci. U. S. A. 91:3911-3915.
36. Su, G., J. Yan, Y. Li, A. Paul, J. Hang, S. Harris, H. Hogg, J. Dunn, C. N. K. Klumpp, and G. Heilek. 2007. In vitro selection and characterization of viruses resistant to R1206 a novel NNRTI. Antivir. Ther. 12(Suppl. 1):S35.
37. Telesnitsky, A., and S. P. Goff. 1998. Reverse transcriptase and the generation of retroviral DNA, p. 121-160. In J. Coffin, H. Varmus, and S. Hughes (ed.), Retroviruses. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.
38. Vingerhoets, J., L. Tambuyzer, H. Azijn, A. Hoogstoel, S. Nijs, M. Peeters, M. P. de Bethune, G. De Smedt, B. Woodfall, and G. Picchio. 2010. Resistance profile of etravirine: combined analysis of baseline genotypic and phenotypic data from the randomized, controlled phase III clinical studies. AIDS 24:503-514.
39. 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.
40. Waheed, A. A., S. D. Ablan, M. K. Mankowski, J. E. Cummins, R. G. Ptak, C. P. Schaffner, and E. O. Freed. 2006. Inhibition of HIV-1 replication by amphotericin B methyl ester: selection for resistant variants. J. Biol. Chem. 281:28699-28711.
41. Wainberg, M. A. 2004. The impact of the M184V substitution on drug resistance and viral fitness. Expert Rev. Anti Infect. Ther. 2:147-151.
42. Wang, J., C. Dykes, R. A. Domaoal, C. E. Koval, R. A. Bambara, and L. M. Demeter. 2006. The HIV-1 reverse transcriptase mutants G190S and G190A, which confer resistance to non-nucleoside reverse transcriptase inhibitors, demonstrate reductions in RNase H activity and DNA synthesis from tRNA(Lys, 3) that correlate with reductions in replication efficiency. Virology 348:462-474.
43. Wei, X., J. M. Decker, H. Liu, Z. Zhang, R. B. Arani, J. M. Kilby, M. S. Saag, X. Wu, G. M. Shaw, and J. C. Kappes. 2002. Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Antimicrob. Agents Chemother. 46:1896-1905.
44. Wei, X., C. Liang, M. Gotte, and M. A. Wainberg. 2002. The M184V mutation in HIV-1 reverse transcriptase reduces the restoration of wild-type replication by attenuated viruses. AIDS 16:2391-2398.
45. Wisniewski, M., C. Palaniappan, Z. Fu, S. F. Le Grice, P. Fay, and R. A. Bambara. 1999. Mutations in the primer grip region of HIV reverse transcriptase can increase replication fidelity. J. Biol. Chem. 274:28175-28184.
46. Wohrl, B. M., R. Krebs, S. H. Thrall, S. F. Le Grice, A. J. Scheidig, and R. S. Goody. 1997. Kinetic analysis of four HIV-1 reverse transcriptase enzymes mutated in the primer grip region of p66. Implications for DNA synthesis and dimerization. J. Biol. Chem. 272:17581-17587.
47. Xu, H. T., J. L. Martinez-Cajas, M. L. Ntemgwa, D. Coutsinos, F. A. Frankel, B. G. Brenner, and M. A. Wainberg. 2009. Effects of the K65R and K65R/ M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Retrovirology 6:14.
48. Zhang, Z., M. Walker, W. Xu, J. H. Shim, J. L. Girardet, R. K. Hamatake, and Z. Hong. 2006. Novel nonnucleoside inhibitors that select nucleoside inhibitor resistance mutations in human immunodeficiency virus type 1 reverse transcriptase. Antimicrob. Agents Chemother. 50:2772-2781.