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

Journal of Virology

Volumn 73, Issue 7, 1999, Pages 5803-5813

  Gerondel, Peter ^a   Archer, Richard H ^a   Palaniappan, Chockalingam ^a,c   Reichman, Richard C ^a   Fay, Philip J ^a   Bambara, Robert A ^a   Demeter, Lisa M ^a,b  

^a UNIVERSITY OF ROCHESTER SCHOOL OF MEDICINE AND DENTISTRY   (United States)

^b UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

^c Amersham Biosciences   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DELAVIRDINE; GAG PROTEIN; RIBONUCLEASE H; VIRUS RNA; ZIDOVUDINE;

ARTICLE; EMBRYO; ENZYME ACTIVITY; ENZYME DEGRADATION; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; PRIORITY JOURNAL; STRUCTURE ANALYSIS; VIRUS MUTATION; VIRUS REPLICATION;

EID: 0032993043     PISSN: 0022538X     EISSN: None     Source Type: Journal    
DOI: 10.1128/jvi.73.7.5803-5813.1999     Document Type: Article

References (54)

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. Arts, E. J., and M. A. Wainberg. 1996. Mechanisms of nucleoside analog antiviral activity and resistance during human immunodeficiency virus reverse transcription. Antimicrob. Agents Chemother. 40:527-540.
3. Ausubel, F. M., R. Brent, R. E. Kingston, D. D. Moore, J. G. Seidman, J. A. Smith, and K. Struhl (ed.). 1997. Current protocols in molecular biology, vol. 2, p. 16.8.6-16.8.8. Wiley & Sons, Inc., New York, N. Y.
4. Avidan, O., and A. Hizi. 1998. The processivity of DNA synthesis exhibited by drug-resistant variants of human immunodeficiency virus type-1 reverse transcriptase. Nucleic Acids Res. 26:1713-1717.
5. 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.
6. Back, N. K. T., and B. Berkhout 1997. Limiting deoxynucleoside triphosphate concentrations emphasize the processivity defect of lamivudine-resistant variants of human immunodeficiency virus type 1 reverse transcriptase. Antimicrob. Agents Chemother. 41:2484-2491.
7. Bambara, R. A., P. J. Fay, and L. M. Mallaber. 1995. Methods of analyzing processivity. Methods Enzymol. 262:270-280.
8. Bebenek, K., and T. A. Kunkel. 1993. The fidelity of retroviral reverse transcriptases. Cold Spring Harbor Monogr. Ser. 5:85-102.
9. Been-Tiktak, A. M., C. J. de Haas, L. de Graaf, C. A. Boucher, J. Verhoef, J. C. Borleffs, H. S. Nottet, and R. Schuurman. 1997. In-vitro selection of HIV-1 variants resistant to non-nucleoside reverse transcriptase inhibitors in monocyte-derived macrophages. J. Antimicrob. Chemother. 40:847-853.
10. Boucher, C. A. B., R. vin Leeuwen, P. Kellam, P. Schipper, J. Tljnagel, J. M A. Lange, and B. A. Larder. 1993. Effects of discontinuation of zidovu-dine treatment on zidovudine sensitivity of human immunodeficiency virus type 1 isolates. Antimicrob. Agents Chemother. 37:1525-1530.
11. Boyer, P. L., A. L. Ferris, P. Clark, J. Whitmer, P. Frank, C. Tantillo, E. Arnold, and S. H. Hughes. 1994. Mutational analysis of the fingers and palm subdomains of human immunodeficiency virus type-1 reverse transcriptase. J. Mol. Biol. 243:472-483.
12. Bradford, M. M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72:248-254.
13. 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.
14. Carpenter, C. C., M. A. Fischl, S. M. Hammer, M. S. Hirsch, D. M. Jacobsen, D. A. Katzenstein, J. S. Montaner, D. D. Richman, M. S. Saag, R. T. Schooley, M. A. Thompson, S. Vella, P. G. Yeni, and P. A. Volberding. 1998. Antiretroviral therapy for HIV infection in 1998: updated recommendations of the International AIDS Society - USA Panel. JAMA 280:78-86.
15. Coffin, J. M. 1995. HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science 267:483-489.
16. Cohen, K. A., J. Hopkins, R. H. Ingraham, C. Pargellis, J. C. Wu, D. E. Palladino, P. Kinkade, T. C. Warren, S. Rogers, J. Adams, et al. 1991. Characterization of the binding site for nevirapine (BI-RG-587), a non-nucleoside inhibitor of human immunodeficiency virus type-1 reverse transcriptase. J. Biol. Chem. 264:14670-14674.
17. Demeter, L. M., R. W. Shafer, P. M. Meehan, J. Holden-Wiltse, M. A. Fischl, W. W. Freimuth, M. Para, and R. C. Reichman. Delavirdine susceptibilities and associated reverse transcriptase mutations in HIV-1 isolates from patients in a phase I/II trial of delavirdine monotherapy (ACTG 260). Submitted for publication.
18. DeStefano, J. J., R. G. Buiser, L. M. Mallaber, T. W. Myers, R. A. Bambara, and P. J. Fay. 1991. Polymerization and RNase H activities of the reverse transcriptases from avian myeloblastosis, human immunodeficiency, and Moloney murine leukemia viruses are functionally uncoupled. J. Biol. Chem. 266:7423-7431.
19. DeStefano, J. J., L. M. Mallaber, P. J. Fay, and R. A. Bambara. 1993. Determinants of the RNase H cleavage specificity of human immunodeficiency virus reverse transcriptase. Nucleic Acids Res. 21:4330-4338.
20. Domingo, E., E. Martinez-Salas, F. Sobrino, J. C. de la Torre, A. Portela, J. Ortin, C. Lopez-Galindez, P. Perez-Brena, N. Villanueva, R. Najera, et al. 1985. The quasispecies (extremely heterogeneous) nature of viral RNA genome populations: biological relevance - a review. Gene 40:1-8.
21. Dueweke, T. J., T. Pushkarskaya, S. M. Poppe, S. M. Swaney, J. Q. Zhao, I. S. Chen, M. Stevenson, and W. G. Tarpley. 1993. A mutation in reverse transcriptase of bis(heteroaryl)piperazine-resistant human immunodeficiency virus type 1 that confers increased sensitivity to other nonnucleoside inhibitors. Proc. Natl. Acad. Sci. USA 90:4713-4717.
22. Esnouf, R., J. Ren, C. Ross, Y. Jones, D. Stammers, and D. Stuart 1995. Mechanism of inhibition of HIV-1 reverse transcriptase by non-nucleoside inhibitors. Nature Struct. Biol. 2:303-308.
23. Esnouf, R. M., J. Ren, A. L. Hopkins, C. K. Ross, E. Y. Jones, D. K. Stammers, and D. I. Stuart. 1997. Unique features in the structure of the complex between HIV-1 reverse transcriptase and the bis(heteroaryl)piperazine (BHAP) U-90152 explain resistance mutations for this nonnucleoside inhibitor. Proc. Natl. Acad. Sci. USA 94:3984-3989.
24. Fuentes, G. M., P. J. Fay, and R. A. Bambara. 1996. Coordination of DNA synthesis and removal of downstream segments of RNA by human immunodeficiency virus, murine leukemia virus, and avian myeloblastosis virus reverse transcriptases. Nucleic Acids Res. 24:1719-1726.
25. Furfine, E. S., and J. E. Reardon. 1991. Reverse transcriptase RNase H from the human immunodeficiency virus: relationship of the DNA polymerase and RNA hydrolysis activities. J. Biol. Chem. 266:406-412.
26. Hirsch, M. S., B. Conway, R. T. D'Aquila, V. A. Johnson, F. Brun-Vezinet, B. Clotet, L. M. Demeter, S. M. Hammer, D. M. Jacobsen, D. R. Kuritzkes, C. Loveday, J. W. Mellors, S. Vella, and D. D. Richman. 1998. Antiretroviral drug resistance testing in adults with HIV infection: implications for clinical management. International AIDS Society - USA Panel. JAMA 279:1984-1991.
27. Ho, D. D., A. U. Neumann, A. S. Perelson, W. Chen, J. M. Leonard, and M. Markowitz. 1995. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373:123-126.
28. Hsu, M., P. Inouye, L. Rezende, N. Richard, Z. Li, V. R. Prasad, and M. A. Wainberg. 1997. Higher fidelity of RNA-dependent DNA mispair extension by M184V drug-resistant than wild-type reverse transcriptase of human immunodeficiency virus type 1. Nucleic Acids Res. 25:4532-4536.
29. Iversen, A. K. N., R. W. Shafer, K. Wehrly, M. A. Winters, J. I. Mullins, B. Chesebro, and T. C. Merigan. 1996. Multidrug-resistant human immunodeficiency virus type 1 strains resulting from combination antiretroviral therapy. J. Virol. 70:1086-1090.
30. Kimpton, J., and M. Emerman. 1992. Detection of replication-competent and pseudotyped human immunodeficiency virus with a sensitive cell line on the basis of activation of an integrated β-galactosidase gene. J. Virol 66: 2232-2239.
31. Kohlstaedt, L. A., J. Wang, J. M. Friedman, P. A. Rice, and T. A. Steitz. 1992. Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 256:1783-1790.
32. Kunkel, T. A., J. D. Roberts, and R. A. Zakour. 1987. Rapid and efficient site-specific mutagenesis without phenotypic selection. Methods Enzymol. 154:367-382.
33. Le Grice, S. F., T. Naas, B. Wohlgensinger, and O. Schatz. 1991. Subunit-selective mutagenesis indicates minimal polymerase activity in heterodimerassociated p51 HIV-1 reverse transcriptase. EMBO J. 10:3905-3911.
34. Loya, S., H.-Q. Gao, O. Avidan, P. L. Boyer, S. H. Hughes, and A. Hizi. 1997. Subunit-specific mutagenesis of the cysteine 280 residue of the reverse transcriptase of human immunodeficiency virus type 1: effects on sensitivity to a specific inhibitor of the RNase H activity. J. Virol. 71:5668-5672.
35. Lu, Y., V. Planelles, X. Li, C. Palaniappan, B. Day, P. Challita-Eid, R. Amado, D. Stephens, D. B. Kohn, A. Bakker, P. Fay, R. A. Bambara, and J. D. Rosenblatt 1997. Inhibition of HIV-1 replication using a mutated tRNALys-3 primer. J. Biol. Chem. 272:14523-14531.
36. Oude Essink, B. B., N. K. Back, and B. Berkhout. 1997. Increased polymerase fidelity of the 3TC-resistant variants of HIV-1 reverse transcriptase. Nucleic Acids Res. 25:3212-3217.
37. Palaniappan, C., P. J. Fay, and R. A. Bambara. 1995. Nevirapine alters the cleavage specificity of ribonuclease H of human immunodeficiency virus 1 reverse transcriptase. J. Biol. Chem. 270:4861-4869.
38. Palaniappan, C., G. M. Fuentes, L. Rodriguez-Rodriguez, P. J. Fay, and R. A. Bambara. 1996. Helix structure and ends of RNA/DNA hybrids direct the cleavage specificity of HIV-1 reverse transcriptase RNase H. J. Biol. Chem. 271:2063-2070.
39. Palaniappan, C., J. K. Kim, M. Wisniewski, P. J. Fay, and R. A. Bambara. 1998. Control of initiation of viral plus strand DNA synthesis by HIV reverse transcriptase. J. Biol. Chem. 273:3808-3816.
40. 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.
41. Pandey, V. N., N. Kaushik, N. Rege, S. G. Sarafianos, P. N. Yadav, and M. J. Modak. 1996. Role of methionine 184 of human immunodeficiency virus type-1 reverse transcriptase in the polymerase function and fidelity of DNA synthesis. Biochemistry 35:2168-2179.
42. Peliska, J. A., and S. J. Benkovic. 1992. Mechanism of DNA strand transfer reactions catalyzed by HIV-1 reverse transcriptase. Science 258:1112-1118.
43. Rausch, J. W., and S. F. J. LeGrice. 1997. Substituting a conserved residue of the ribonuclease H domain alters substrate hydrolysis by retroviral reverse transcriptase. J. Biol. Chem. 272:8602-8610.
44. Richman, D. D., D. Havlir, J. Corbeil, D. Looney, C. Ignacio, S. A. Spector, J. Sullivan, S. Cheeseman, K. Barringer, D. Pauletti, C.-K. Shih, M. Myers, and J. Griffin. 1994. Nevirapine resistance mutations of human immunodeficiency virus type 1 selected during therapy. J. Virol. 68:1660-1666.
45. Rubinek, T., M. Bakhanashvili, R. Taube, O. Avidan, and A. Hizi. 1997. The fidelity of 3′ misinsertion and mispair extension during DNA synthesis exhibited by two drug-resistant mutants of the reverse transcriptase of human immunodeficiency virus type 1 with Leu74-→Val and Glu89→Gly. Eur. J. Biochem. 247:238-247.
46. Sharma, P. L., and C. S. Crumpacker. 1997. Attenuated replication of human immunodeficiency virus type 1 with a didanosine-selected reverse transcriptase mutation. J. Virol. 71:8846-8851.
47. 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. USA 91:3911-3915.
48. Spence, R. A., K. S. Anderson, and K. A. Johnson. 1996. HIV-1 reverse transcriptase resistance to nonnucleoside inhibitors. Biochemistry 35:1054-1063.
49. Staszewski, S., J. Morales-Ramirez, T. Flanigan, D. Hardy, P. Johnson, M. Nelson, and N. Ruiz. 1998. A phase II, multi center, randomized, open-label study to compare the antiretroviral activity and tolerability of efavirenz (EFV) + indinavir (IDV), versus EFV + zidovudine (ZDV) + lamivudine (3TC), versus IDV + ZDV + 3TC at 24 weeks (DMP 266-006), abstr. 22336. In Proceedings of the 12th World AIDS Conference.
50. Wainberg, M. A. 1997. Increased fidelity of drug-selected M184V mutated HIV-1 reverse transcriptase as the basis for the effectiveness of 3TC in HIV clinical trials. Leukemia 11(Suppl. 3):85-88.
51. Wainberg, M. A., W. C. Drosopoulos, H. Salomon, M. Hsu, G. Borkow, M. Parniak, Z. Gu, Q. Song, J. Manne, S. Islam, G. Castriota, and V. R. Prasad. 1996. Enhanced fidelity of 3TC-selected mutant HIV-1 reverse transcriptase. Science 271:1282-1285.
52. Wei, X., S. K. Ghosh, M. E. Taylor, V. A. Johnson, E. A. Emini, P. Deutsch, J. D. Lifson, S. Bonhoeffer, M. A. Nowak, B. H. Hahn, et al. 1995 Viral dynamics in human immunodeficiency virus type 1 infection. Nature 373: 117-122.
53. Whitcomb, J. M., and S. H. Hughes. 1992. Retroviral reverse transcription and integration: progress and problems. Annu. Rev. Cell Biol. 8:275-306.
54. World Health Organization. 1998. The current global situation of the HIV/ AIDS pandemic. World Health Organization, Geneva, Switzerland.