Identification of a key target sequence to block human immunodeficiency virus type 1 replication within the gag-pol transframe domain

Journal of Virology

Volumn 74, Issue 10, 2000, Pages 4621-4633

  Sei, Shizuko ^a   Yang, Quan En ^a   O'Neill, Dennis ^a   Yoshimura, Kazuhisa ^b,d   Nagashima, Kunio ^a   Mitsuya, Hiroaki ^a,b,c  

^a SAIC FREDERICK INC   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

^c KUMAMOTO UNIV SCHOOL OF MEDICINE   (Japan)

^d KUMAMOTO UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

GAG PROTEIN; POL PROTEIN;

ANIMAL CELL; ARTICLE; CARBOXY TERMINAL SEQUENCE; CONTROLLED STUDY; DNA FLANKING REGION; GENE DISRUPTION; GENE EXPRESSION; GENE SEQUENCE; GENE TARGETING; GENETIC CONSERVATION; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; RNA TRANSLATION; VIRION; VIRUS GENE; VIRUS REPLICATION;

3' UNTRANSLATED REGIONS; ANTI-HIV AGENTS; BASE SEQUENCE; CELL LINE; CELLS, CULTURED; ENZYME ACTIVATION; FUSION PROTEINS, GAG-POL; GENE PRODUCTS, GAG; GENE TARGETING; HIV CORE PROTEIN P24; HIV INFECTIONS; HIV PROTEASE; HIV-1; HUMANS; MOLECULAR SEQUENCE DATA; PEPTIDE NUCLEIC ACIDS; PROTEIN PRECURSORS; VIRION; VIRUS REPLICATION;

EID: 0034001718     PISSN: 0022538X     EISSN: None     Source Type: Journal    
DOI: 10.1128/JVI.74.10.4621-4633.2000     Document Type: Article

References (155)

1. Aalen, O. O., V. T. Farewell, D. De Angelis, N. E. Day, and O. N. Gill. 1999. New therapy explains the fall in AIDS incidence with a substantial rise in number of persons on treatment expected. AIDS 13:103-108.
2. Agrawal, S., T. Ikeuchi, D. Sun, P. S. Sarin, A. Konopka, J. Maizel, and P. C. Zamecnik. 1989. Inhibition of human immunodeficiency virus in early infected and chronically infected cells by antisense oligodeoxynucleotides and their phosphorothioate analogues. Proc. Natl. Acad. Sci. USA 86: 7790-7794.
3. Aldrovandi, G. M., and J. A. Zack. 1996. Replication and pathogenicity of human immunodeficiency virus type 1 accessory gene mutants in SCID-hu mice. J. Virol. 70:1505-1511.
4. Anazodo, M. I., E. Duta, A. D. Friesen, and J. A. Wright. 1996. Relative levels of inhibition of p24 gene expression by different 20-mer antisense oligonucleotide sequences targeting nucleotides + 1129 to + 1268 of the HIV-1 gag genome: an analysis of mechanism. Biochem. Biophys. Res. Commun. 229:305-309.
5. Anazodo, M. I., M. A. Wainberg, A. D. Friesen, and J. A. Wright. 1995. Sequence-specific inhibition of gene expression by a novel antisense oligodeoxynucleotide phosphorothioate directed against a nonregulatory region of the human immunodeficiency virus type 1 genome. J. Virol. 69: 1794-1801.
6. Aoki-Sei, S., R. Yarchoan, S. Kageyama, D. Hoekzema, J. M. Pluda, K. M. Wyvill, S. Broder, and H. Mitsuya. 1992. Plasma HIV-1 viremia in HIV-1 infected individuals assessed by polymerase chain reaction. AIDS Res. Hum. Retrovir. 8:1263-1270.
7. Artico, M., R. Di Santo, R. Costi, E. Novellino, G. Greco, S. Massa, E. Tramontane, M. E. Marongiu, A. De Montis, and P. La Colla. 1998. Geometrically and conformationally restrained cinnamoyl compounds as inhibitors of HIV-1 integrase: synthesis, biological evaluation, and molecular modeling. J. Med. Chem. 41:3948-3960.
8. Barrie, K. A., E. E. Perez, S. L. Lamers, W. G. Farmerie, B. M. Dunn, J. W. Sleasman, and M. M. Goodenow. 1996. Natural variation in HIV-1 protease, Gag p7 and p6, and protease cleavage sites within gag/pol polyproteins: amino acid substitutions in the absence of protease inhibitors in mothers and children infected by human immunodeficiency virus type 1. Virology 219:407-416.
9. Boiziau, C., N. T. Thuong, and J. J. Toulme. 1992. Mechanisms of the inhibition of reverse transcription by antisense oligonucleotides. Proc. Natl. Acad. Sci. USA 89:768-772.
10. Bonham, M. A., S. Brown, A. L. Boyd, P. H. Brown, D. A. Bruckenstein, J. C. Hanvey, S. A. Thomson, A. Pipe, F. Hassman, J. E. Bisi, et al. 1995. An assessment of the antisense properties of RNase H-competent and stericblocking oligomers. Nucleic Acids Res. 23:1197-1203.
11. Borsetti, A., A. Ohagen, and H. G. Gottlinger. 1998. The C-terminal half of the human immunodeficiency virus type 1 Gag precursor is sufficient for efficient particle assembly. J.Virol. 72:9313-9317.
12. Brierley, I., M. E. Bonrsnell, M. M. Binns, B. Bilimoria, V. C. Blok, T. D. Brown, and S. C. Inglis. 1987. An efficient ribosomal frame-shifting signal in the polymerase-encoding region of the coronavirus IBV. EMBO J. 6: 3779-3785.
13. Bryant, M., and L. Ratner. 1990. Myristoylation-dependent replication and assembly of human immunodeficiency virus 1. Proc. Natl. Acad. Sci. USA 87:523-527.
14. Cazenave, C., C. A. Stein, N. Loreau, N. T. Thuong, L. M. Neckers, C. Subasinghe, C. Helene, J. S. Cohen, and J. J. Toulme. 1989. Comparative inhibition of rabbit globin mRNA translation by modified antisense oligodeoxynucleotides. Nucleic Acids Res. 17:4255-4273.
15. Centers for Disease Control and Prevention. 1998. HIV/AIDS surveillance report, midyear ed. vol. 10. Centers for Disease Control and Prevention. Public Health Service, Department of Health and Human Services, Atlanta, Ga.
16. Chackerian, B., E. M. Long, P. A. Luciw, and J. Overbaugh. 1997. Human immunodeficiency virus type 1 coreceptors participate in postentry stages in the virus replication cycle and function in simian immunodeficiency virus infection. J. Virol. 71:3932-3939.
17. Checroune, F., X. J. Yao, H. G. Gottlinger, D. Bergeron, and E. A. Cohen. 1995. Incorporation of Vpr into human immunodeficiency virus type 1: role of conserved regions within the P6 domain of Pr55gag. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 10:1-7.
18. Chun, T. W., D. Engel, M. M. Berrey, T. Shea, L. Corey, and A. S. Fauci. 1998. Early establishment of a pool of latently infected, resting CD4(+) T cells during primary HIV-1 infection. Proc. Natl. Acad. Sci. USA 95:8869-8873.
19. Chun, T. W., L. Stuyver, S. B. Mizell, L. A. Ehler, J. A. Mican, M. Baseler, A. L. Lloyd, M. A. Nowak, and A. S. Fauci. 1997. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc. Natl. Acad. Sci. USA 94:13193-13197.
20. Collier, A. C., R. W. Coombs, D. A. Schoenfeld, R. L. Bassett, J. Timpone, A. Baruch, M. Jones, K. Facey, C. Whitacre, V. J. McAuliffe, H. M. Friedman, T. C. Merigan, R. C. Reichman, C. Hooper, and L. Corey. 1996. Treatment of human immunodeficiency virus infection with saquinavir, zidovudine, and zalcitabine. AIDS Clinical Trials Group. N. Engl. J. Med. 334:1011-1017.
21. Condra, J. H., W. A. Schleif, O. M. Blahy, L. J. Gabryelski, D. J. Graham, J. C. Quintero, A. Rhodes, H. L. Robbins, E. Roth, M. Shivaprakash, et al. 1995. In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors. Nature 374:569-571.
22. Danner, S. A., A. Carr, J. M. Leonard, L. M. Lehman, F. Gudiol, J. Gonzales, A. Raventos, R. Rubio, E. Bouza, V. Pintado, et al. 1995. A short-term study of the safety, pharmacokinetics, and efficacy of ritonavir, an inhibitor of HIV-1 protease. European-Australian Collaborative Ritonavir Study Group. N. Engl. J. Med. 333:1528-1533.
23. De Clercq, E. 1992. HIV inhibitors targeted at the reverse transcriptase. AIDS Res Hum. Retrovir. 8:119-134.
24. Demidov, V, V., V. N. Potaman, M. D. Frank-Kamenetskii, M. Egholm, O. Buchard, S. H. Sonnichsen, and P. E. Nielsen. 1994. Stability of peptide nucleic acids in human serum and cellular extracts. Biochem. Pharmacol. 48:1310-1313.
25. Donzella, G. A., D. Schols, S. W. Lin, J. A. Este, K. A. Nagashima, P. J. Maddon, G. P. Allaway, T. P. Sakmar, G. Henson, E. De Clercq, and J. P. Moore. 1998. AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor. Nat. Med. 4:72-77.
26. Doranz, B. J., K, Grovit-Ferbas, M. P. Sharron, S. H. Mao, M. B. Goetz, E. S. Daar, R. W. Doms, and W. A. O'Brien. 1997. A small-molecule inhibitor directed against the chemokine receptor CXCR4 prevents its use as an HIV-1 coreceptor. J. Exp. Med. 186:1395-1400.
27. Egholm, M., O. Buchardt, L. Christensen, C. Behrens, S. M. Freier, D. A. Driver, R. H. Berg, S. K. Kim, B. Norden, and P. E. Nielsen. 1993. PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen-bonding rules. Nature 365:566-568.
28. Egholm, M., O. Buchardt, P. E. Nielsen, and R. H. Berg. 1992. Peptide nucleic acids (PNA). Oligonucleotide analogues with an achiral peptide backbone. J. Am. Chem. Soc. 114:1895-1897.
29. Eich, E., H. Pertz, M. Kaloga, J. Schulz, M. R. Fesen, A. Mazumder, and Y. Pommier. 1996. ( - )-Arctigenin as a lead structure for inhibitors of human immunodeficiency virus type-1 integrase. J. Med. Chem. 39:86-95.
30. Falk, H., N. Mador, R. Udi, A. Panet, and A, Honigman. 1993. Two cisacting signals control ribosomal frameshift between human T-cell leukemia virus type II gag and pro genes. J. Virol. 67:6273-6277.
31. Farnet, C. M., B. Wang, M. Hansen, J. R. Lipford, L. Zalkow, W. E. Robinson, Jr., J. Siegel, and F. Bushman. 1998. Human immunodeficiency virus type 1 cDNA integration: new aromatic hydroxylated inhibitors and studies of the inhibition mechanism. Antimicrob. Agents Chemother. 42: 2245-2253.
32. Felber, B. K., C. M. Drysdale, and G. N. Pavlakis. 1990. Feedback regulation of human immunodeficiency virus type 1 expression by the Rev protein. J. Virol. 64:3734-3741.
33. Finzi, D., M. Hermankova, T. Pierson, L. M. Carruth, C. Buck, R. E. Chaisson, T. C. Quinn, K. Chadwick, J. Margolick, R. Brookmeyer, J. Gallant, M. Markowitz, D. D. Ho, D. D. Richman, and R. F. Siliciano. 1997. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278:1295-1300.
34. Flexner, C., S. S. Broyles, P. Earl, S. Chakrabarti, and B. Moss. 1988. Characterization of human immunodeficiency virus gag/pol gene products expressed by recombinant vaccinia viruses. Virology 166:339-349.
35. Freed, E. O., J. M. Orenstein, A. J. Buckler-White, and M. A. Martin. 1994. Single amino acid changes in the human immunodeficiency virus type 1 matrix protein block virus particle production. J. Virol. 68:5311-5320.
36. Furtado, M. R., D. S. Callaway, J. P. Phair, K. J. Kunstman, J. L. Stanton, C. A. Macken, A. S. Perelson, and S. M. Wolinsky. 1999. Persistence of HIV-1 transcription in peripheral-blood mononuclear cells in patients receiving potent antiretroviral therapy. N. Engl. J. Med. 340:1614-1622.
37. Gibbs, J. S., D. A. Regier, and R. C. Desrosiers. 1994. Construction and in vitro properties of HIV-1 mutants with deletions in "nonessential" genes. AIDS Res. Hum. Retrovir. 10:343-350.
38. Gonda, M. A., F. Wong-Staal, R. C. Gallo, J. E. Clements, O. Narayan, and R. V. Gilden. 1985. Sequence homology and morphologic similarity of HTLV-III and visna virus, a pathogenic lentivirus. Science 227:173-177.
39. Gong, W., O. M. Howard, J. A. Turpin, M. C. Grimm, H. Ueda, P. W. Gray, C. J. Raport, J. J. Oppenheim, and J. M. Wang. 1998. Monocyte chemotactic protein-2 activates CCR5 and blocks CD4/CCR5-mediated HIV-1 entry/replication. J. Biol. Chem. 273:4289-4292.
40. Gottlinger, H. G., T. Dorfman, J. G. Sodroski, and W. A. Haseltine. 1991. Effect of mutations affecting the p6 gag protein on human immunodeficiency virus particle release. Proc. Natl. Acad. Sci. USA 88:3195-3199.
41. Gottlinger, H. G., J. G. Sodroski, and W. A. Haseltine. 1989. Role of capsid precursor processing and myristoylation in morphogenesis and infectivity of human immunodeficiency virus type 1. Proc. Natl. Acad. Sci. USA 86: 5781-5785.
42. Gray, G. D., S. Basu, and E. Wickstrom. 1997. Transformed and immortalized cellular uptake of oligodeoxynucleoside phosphorothioates, 3'-alkylamino oligodeoxynucleotides, 2'-O-methyl oligoribonucleotides, oligodeoxynucleoside methylphosphonates, and peptide nucleic acids. Biochem. Pharmacol. 53:1465-1476.
43. Gulick, R. M., J. W. Mellors, D. Havlir, J. J. Eron, C. Gonzalez, D. McMahon, D. D. Richman, F. T. Valentine, L. Jonas, A. Meibohm, E. A. Emini, and J. A. Chodakewitz. 1997. Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. N. Engl. J. Med. 337:734-739.
44. Hammer, S. M., K. E. Squires, M. D. Hughes, J. M. Grimes, L. M. Demeter, J. S. Currier, J. J. Eron, Jr., J. E. Feinberg, H. H. Balfour, Jr., L. R. Deyton, J. A. Chodakewitz, and M. A. Fischl. 1997. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N. Engl. J. Med. 337:725-733.
45. Hanvey, J. C., N. J. Peffer, J. E. Bisi, S. A. Thomson, R. Cadilla, J. A. Josey, D. J. Ricca, C. F. Hassman, M. A. Bonham, K. G. Au, et al. 1992. Antisense and antigene properties of peptide nucleic acids. Science 258:1481-1485.
46. Hargrave, K. D., J. R. Proudfoot, K. G. Grozinger, E. Cullen, S. R. Kapadia, U. R. Patel, V. U. Fuchs, S. C. Mauldin, J. Vitous, M. L. Behnke, et al. 1991. Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase. 1. Tricyclic pyridobenzo- and dipyridodiazepinones. J. Med. Chem. 34:2231-2241.
47. 2-symmetric protease inhibitor. J. Virol. 68:2016-2020.
48. gag-pol into virus particles requires the presence of both the major homology region and adjacent C-terminal capsid sequences within the Gag-Pol polyprotein. J. Virol. 71:4472-4478.
49. Huang, M., J. M. Orenstein, M. A. Martin, and E. O. Freed. 1995. p6Gag is required for particle production from full-length human immunodeficiency virus type 1 molecular clones expressing protease. J. Virol. 69: 6810-6818.
50. Husson, R. N., T. Shirasaka, K. M. Butler, P. A. Pizzo, and H. Mitsuya. 1993. High-level resistance to zidovudine but not to zalcitabine or didanosine in human immunodeficiency virus from children receiving antiretroviral therapy. J. Pediatr. 123:9-16.
51. Igloi, G. L. 1998. Variability in the stability of DNA-peptide nucleic acid (PNA) single-base mismatched duplexes: real-time hybridization during affinity electrophoresis in PNA-containing gels. Proc. Natl. Acad. Sci. USA 95:8562-8567.
52. Jacks, T., M. D. Power, F. R. Masiarz, P. A. Luciw, P. J. Barr, and H. E. Varmus. 1988. Characterization of ribosomal frameshifting in HIV-1 gagpol expression. Nature 331:280-283.
53. Jacks, T., K. Townsley, H. E. Varmus, and J. Majors. 1987. Two efficient ribosomal frameshifting events are required for synthesis of mouse mammary tumor virus gag-related polyproteins. Proc. Natl. Acad. Sci. USA 84: 4298-4302.
54. Jacks, T., and H. E. Varmus. 1985. Expression of the Rous sarcoma virus pol gene by ribosomal frameshifting. Science 230:1237-1242.
55. Johnson, V. A., D. P. Merrill, T. C. Chou, and M. S. Hirsch. 1992. Human immunodeficiency virus type 1 (HIV-1) inhibitory interactions between protease inhibitor Ro 31-8959 and zidovudine, 2',3'-dideoxycytidine, or recombinant interferon-alpha A against zidovudine-sensitive or -resistant HIV-1 in vitro. J. Infect. Dis. 166:1143-1146.
56. Kageyama, S., T. Mimoto, Y. Murakawa, M. Momizu, H. Ford, Jr., T. Shirasaka, S. Gulnik, J. Erickson, K. Takada, H. Hayashi, S. Broder, Y. Kiso, and H. Mitsuya. 1993. In vitro anti-human immunodeficiency virus (HIV) activities of transition state mimetic HIV protease inhibitors containing allophenylnorstatine. Antimicrob. Agents Chemother. 37:810-817.
57. 2 symmetrybased HIV protease inhibitors as single agents or in combinations. Antimicrob. Agents Chemother. 36:926-933.
58. Kaplan, A. H., M. Manchester, and R. Swanstrom. 1994. The activity of the protease of human immunodeficiency virus type 1 is initiated at the membrane of infected cells before the release of viral proteins and is required for release to occur with maximum efficiency. J. Virol. 68:6782-6786.
59. Kaplan, A. H., and R. Swanstrom. 1991. Human immunodeficiency virus type 1 Gag proteins are processed in two cellular compartments. Proc. Natl. Acad. Sci. USA 88:4528-4532.
60. Karacostas, V., E. J. Wolffe, K. Nagashima, M. A. Gonda, and B. Moss. 1993. Overexpression of the HIV-1 gag-pol polyprotein results in intracellular activation of HIV-1 protease and inhibition of assembly and budding of virus-like particles. Virology 193:661-671.
61. Kavlick, M. F., T. Shirasaka, E. Kojima, J. M. Pluda, F. Hui, Jr., R. Yarchoan, and H. Mitsuya. 1995. Genotypic and phenotypic characterization of HIV-1 isolated from patients receiving (-)-2',3'-dideoxy-3'-thiacytidine. Antivir. Res. 28:133-146.
62. Kavlick, M. F., K. Wyvill, R. Yarchoan, and H. Mitsuya. 1998. Emergence of multi-dideoxynucleoside-resistant human immunodeficiency virus type 1 variants, viral sequence variation, and disease progression in patients receiving antiretroviral chemotherapy. J. Infect. Dis. 177:1506-1513.
63. Kempf, D. J., K. C. Marsh, J. F. Denissen, E. McDonald, S. Vasavanonda, C. A. Flentge, B. E. Green, L. Fino, C. H. Park, X. P. Kong, et al. 1995. ABT-538 is a potent inhibitor of human immunodeficiency virus protease and has high oral bioavailability in humans. Proc. Natl. Acad. Sci. USA 92: 2484-2488.
64. Kim, S. G., T. Hatta, S. Tsukahara, H. Nakashima, N. Yamamoto, Y. Shoji, K. Takai, and H. Takaku. 1995. Antiviral effect of phosphorothioate oligodeoxyribonucleotides complementary to human immunodeficiency virus. Bioorg. Med. Chem. 3:49-54.
65. 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 beta-galactosidase gene. J. Virol. 66:2232-2239.
66. Kinchington, D., S. Galpin, J. W. Jaroszewski, K, Ghosh, C. Subasinghe, and J. S. Cohen. 1992. A comparison of gag, pol and rev antisense oligodeoxyrmcleotides as inhibitors of HIV-1. Antivir. Res. 17:53-62.
67. Kojima, E., T. Shirasaka, B. D. Anderson, S. Chokekijchai, S. M. Steinberg, S. Broder, R. Yarchoan, and H. Mitsuya. 1995. Human immunodeficiency virus type 1 (HIV-1) viremia changes and development of drug-related mutations in patients with symptomatic HIV-1 infection receiving alternating or simultaneous zidovudine and didanosine therapy. J. Infect. Dis. 171: 1152-1158.
68. gag required for the incorporation of human immunodeficiency virus type 1 Vpr. J. Virol. 70:159-164.
69. Koppelhus, U., V. Zachar, P. E. Nielsen, X. Liu, J. Eugen-Olsen, and P. Ebbesen. 1997. Efficient in vitro inhibition of HIV-1 gag reverse transcription by peptide nucleic acid (PNA) at minimal ratios of PNA/RNA. Nucleic Acids Res. 25:2167-2173.
70. Kozak, M. 1984. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Res. 12:857-872.
71. Kozak, M. 1980. Evaluation of the "scanning model" for initiation of protein synthesis in eucaryotes. Cell 22:7-8.
72. Kozak, M. 1986. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell 44: 283-292.
73. Kozak, M. 1981. Possible role of flanking nucleotides in recognition of the AUG initiator codon by eukaryotic ribosomes. Nucleic Acids Res. 9:5233-5262.
74. Kozak, M. 1989. The scanning model for translation: an update. J. Cell Biol. 108:229-241.
75. Kozak, M. 1984. Selection of initiation sites by eucaryotic ribosomes: effect of inserting AUG triplets upstream from the coding sequence for preproinsulin. Nucleic Acids Res. 12:3873-3893.
76. Kozal, M. J., N. Shah, N. Shen, R. Yang, R. Fucini, T. C. Merigan, D. D. Richman, D. Morris, E. Hubbell, M. Chee, and T. R. Gingeras. 1996. Extensive polymorphisms observed in HIV-1 clade B protease gene using high-density oligonucleotide arrays. Nat. Med. 2:753-759.
77. Lam, P. Y., P. K. Jadhav, C. J. Eyermann, C. N. Hodge, Y. Ru, L. T. Bacheler, J. L. Meek, M. J. Otto, M. M. Rayner, Y. N. Wong, et al. 1994. Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease inhibitors. Science 263:380-384.
78. Larder, B. A., G. Darby, and D. D. Richman. 1989. HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. Science 243:1731-1734.
79. Lech, W. J., G. Wang, Y. L. Yang, Y. Chee, K. Dorman, D. McCrae, L. C. Lazzeroni, J. W. Erickson, J. S. Sinsheimer, and A. H. Kaplan. 1996. In vivo sequence diversity of the protease of human immunodeficiency virus type 1: presence of protease inhibitor-resistant variants in untreated subjects. J. Virol. 70:2038-2043.
80. Lee, Y. M., C. J. Tian, and X. F. Yu. 1998. A bipartite membrane-binding signal in the human immunodeficiency virus type 1 matrix protein is required for the proteolytic processing of Gag precursors in a cell typedependent manner. J. Virol. 72:9061-9068.
81. Lee, Y. M., and X. F. Yu. 1998. Identification and characterization of virus assembly intermediate complexes in HIV-1-infected CD4+ T cells. Virology 243:78-93.
82. Liang, C., L. Rong, M. Laughrea, L. Kleiman, and M. A. Wainberg. 1998. Compensatory point mutations in the human immunodeficiency virus type 1 Gag region that are distal from deletion mutations in the dimerization initiation site can restore viral replication. J. Virol. 72:6629-6636.
83. Lisziewicz, J., D. Sun, M. Klotman, S. Agrawal, P. Zamecnik, and R. Gallo. 1992. Specific inhibition of human immunodeficiency virus type 1 replication by antisense oligonucleotides: an in vitro model for treatment. Proc. Natl. Acad. Sci. USA 89:11209-11213.
84. Lisziewicz, J., D. Sun, A. Lisziewicz, and R. C. Gallo. 1995. Antitat gene therapy: a candidate for late-stage AIDS patients. Gene Ther. 2:218-222.
85. Lisziewicz, J., D. Sun, V. Metelev, P. Zamecnik, R. C. Gallo, and S. Agrawal. 1993. Long-term treatment of human immunodeficiency virusinfected cells with antisense oligonucleotide phosphorothioates. Proc. Natl. Acad. Sci. USA 90:3860-3864.
86. Lisziewicz, J., D. Sun, F. F. Weichold, A. R. Thierry, P. Lusso, J. Tang, R. C. Gallo, and S. Agrawal. 1994. Antisense oligodeoxynucleotide phosphorothioate complementary to Gag mRNA blocks replication of human immunodeficiency virus type 1 in human peripheral blood cells. Proc. Natl. Acad. Sci. USA 91:7942-7946.
87. Lowe, D. M., A. Aitken, C. Bradley, G. K. Darby, B. A. Larder, K. L. Powell, D. J. Purifoy, M. Tisdale, and D. K. Stammers. 1988. HIV-1 reverse transcriptase: crystallization and analysis of domain structure by limited proteolysis. Biochemistry 27:8884-8889.
88. gag is important for Vpr incorporation into human immunodeficiency virus type 1 particles. J. Virol. 69: 6873-6879.
89. Mador, N., A. Panet, and A. Honigman. 1989. Translation of gag, pro, and pol gene products of human T-cell leukemia virus type 2. J. Virol. 63: 2400-2404.
90. Markowitz, M., H. Mo, D. J. Kempf, D. W. Norbeck, T. N. Bhat, J. W. Erickson, and D. D. Ho. 1995. Selection and analysis of human immunodeficiency virus type 1 variants with increased resistance to ABT-538, a novel protease inhibitor. J. Virol. 69:701-706.
91. Markowitz. M., M. Saag, W. G. Powderly, A. M. Hurley, A. Hsu, J. M. Valdes, D. Henry, F. Sattler, A. La Marca, J. M. Leonard, et al. 1995. A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection. N. Engl. J. Med. 333:1534-1539.
92. Matsukura, M., G. Zon, K. Shinoznka, M. Robert-Guroff, T. Shimada, C. A. Stein, H. Mitsuya, F. Wong-Staal, J. S. Cohen, and S. Broder. 1989. Regulation of viral expression of human immunodeficiency virus in vitro by an antisense phosphorothioate oligodeoxynucleotide against rev (art/trs) in chronically infected cells. Proc. Natl. Acad. Sci. USA 86:4244-4248.
93. Mazumder, A., N. Neamati, J. O. Ojwang, S. Sunder, R. F. Rando, and Y. Pommier. 1996. Inhibition of the human immunodeficiency virus type 1 integrase by guanosine quartet structures. Biochemistry 35:13762-13771.
94. McDonnell, N. B., R. N. De Guzman, W. G. Rice, J. A. Turpin, and M. F. Summers. 1997. Zinc ejection as a new rationale for the use of cystamine and related disulfide-containing antiviral agents in the treatment of AIDS. J. Med. Chem. 40:1969-1976.
95. Mitsuya, H., and S. Broder. 1986. Inhibition of the in vitro infectivity and cytopathic effect of human T-lymphotrophic virus type III/lymphadenopathy-associaled virus (HTLV-III/LAV) by 2',3'-dideoxynucleosides. Proc. Natl. Acad. Sci. USA 83:1911-1915.
96. Mitsuya, H., R. F. Jarrett, M. Matsukura, F. Di Marzo Veronese, A. L. DeVico, M. G. Sarngadharan, D. G. Johns, M. S. Reitz, and S. Broder. 1987. Long-term inhibition of human T-lymphotropic virus type III/lymphadenopathy-associated virus (human immunodeficiency virus) DNA synthesis and RNA expression in T cells protected by 2',3'-dideoxynucleosides in vitro. Proc. Natl. Acad. Sci. USA 84:2033-2037.
97. Mitsuya, H., K. J. Weinhold, P. A. Furman, M. H. St. Clair, S. N. Lehrman, R. C. Gallo, D. Bolognesi, D. W. Barry, and S. Broder. 1985. 3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc. Natl. Acad. Sci. USA 82:7096-7100.
98. Moore, R., M. Dixon, R. Smith, G. Peters, and C. Dickson. 1987. Complete nucleotide sequence of a milk-transmitted mouse mammary tumor virus: two frameshift suppression events are required for translation of gag and pol. J. Virol. 61:480-490.
99. Murakami, T., T. Nakajima, Y. Koyanagi, K. Tachibana, N. Fujii, H. Tamamura, N. Yoshida, M. Waki, A. Matsumoto, O. Yoshie, T. Kishimoto, N. Yamamoto, and T. Nagasawa. 1997. A small molecule CXCR4 inhibitor that blocks T cell line-tropic HIV-1 infection. J. Exp. Med. 186:1389-1393.
100. Nam, S. H., T. D. Copeland, M. Hatanaka, and S. Oroszlan. 1993. Characterization of ribosomal frameshifting for expression of pol gene products of human T-cell leukemia virus type 1. J. Virol. 67:196-203.
101. Neamati, N., H. Hong, J. M. Owen, S. Sunder, H. E. Winslow, J. L. Christensen, H. Zhao, T. R. Burke, Jr., G. W. Milne, and Y. Pommier. 1998. Salicylhydrazine-containing inhibitors of HIV-1 integrase: implication for a selective chelation in the integrase active site. J. Med. Chem. 41:3202-3209.
102. Neumann, M., J. Harrison, M. Saltarelli, E. Hadziyannis, V. Erfle, B. K. Felber, and G. N. Pavlakis. 1994. Splicing variability in HIV type 1 revealed by quantitative RNA polymerase chain reaction. AIDS Res. Hum. Retrovir. 10:1531-1542.
103. Nielsen, P. E., M. Egholm, R. H. Berg, and O. Buchardt. 1991. Sequenceselective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science 254:1497-1500.
104. Noble, S. A., M. A. Bonham, J. E. Bisi, D. A. Bruckenstein, P. H. Brown, S. C. Brown, R. Cadilla, M. D. Gaul, J. C. Hanvey, C. F. Hassman. J. A. Josey, M. J. Luzzio, P. M. Myers, A. J. Pipe, D. J. Ricca, C. W. Su, C. L. Stevenson, S. A. Thomson, R. W. Wiethe, and L. E. Babiss. 1995. Impact of biophysical parameters on the biological assessment of peptide nucleic acids, antisense inhibitors of gene expression. Drug Dev. Res. 34:184-195.
105. Oberlin, E., A. Amara, F. Bachelerie, C. Bessia, J. L. Virelizier, F. Arenzana-Seisdedos, O. Schwartz, J. M. Heard, I. Clark-Lewis, D. F. Legler, M. Loetscher, M. Baggiolini, and B. Moser. 1996. The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature 382:833-835. (Erratum, 384:288.)
106. Gag protein of Moloney murine leukemia virus. J. Virol. 72:2962-2968.
107. Otto, M. J., S. Garber, D. L. Winslow, C. D. Reid, P. Aldrich, P. K. Jadhav, C. E. Patterson, C. N. Hodge, and Y. S. Cheng. 1993. In vitro isolation and identification of human immunodeficiency virus (HIV) variants with reduced sensitivity to C-2 symmetrical inhibitors of HIV type 1 protease. Proc. Natl. Acad. Sci. USA 90:7543-7547.
108. gag and is incorporated into viruslike particles. J. Virol. 66:6304-6313.
109. Park, J., and C. D. Morrow. 1991. Overexpression of the gag-pol precursor from human immunodeficiency virus type 1 proviral genomes results in efficient proteolytic processing in the absence of virion production. J. Virol. 65:5111-5117.
110. Partaledis, J. A., K. Yamaguchi, M. Tisdale, E. E. Blair, C. Falcione, B. Maschera, R. E. Myers, S. Pazhanisamy, O. Futer, A. B. Cullinan, C. M. Stuver, R. A. Byrn, and D. J. Livingston. 1995. In vitro selection and characterization of human immunodeficiency virus type 1 (HIV-1) isolates with reduced sensitivity to hydroxyethylamino sulfonamide inhibitors of HIV-1 aspartyl protease. J. Virol. 69:5228-5235.
111. Patick, A. K., R. Rose, J. Greytok, C. M. Bechtold, M. A. Hermsmeier, P. T. Chen, J. C. Barrish. R. Zahler, R. J. Colonno, and P. F. Lin. 1995. Characterization of human immunodeficiency virus type 1 variant with reduced sensitivity to an aminodiol protease inhibitor. J. Virol. 69:2148-2152.
112. Pearl, L. H., and W. R. Taylor. 1987. A structural model for the retroviral proteases. Nature 329:351-354.
113. Pooga, M., M. Hallbrink, M. Zorko, and U. Langel. 1998. Cell penetration by transportan. FASEB J. 12:67-77.
114. Pooga, M., U. Soomets, M. Hallbrink, A. Valkna, K. Saar, K. Rezaei, U. Kahl. J. X. Hao, X. J. Xu, Z. Wiesenfeld-Hallin, T. Hokfelt, T. Bartfai, and U. Langel. 1998. Cell penetrating PNA constructs regulate galanin receptor levels and modify pain transmission in vivo. Nat. Biotechnol. 16:857-861.
115. Puras Lutzke, R. A., N. A. Eppens, P. A. Weber, R. A. Houghten, and R. H. Plasterk. 1995. Identification of a hexapeptide inhibitor of the human immunodeficiency virus integrase protein by using a combinatorial chemical library. Proc. Natl. Acad. Sci. USA 92:11456-11460.
116. Rhee, S. S., and E. Hunter. 1987. Myristylation is required for intracellular transport but not for assembly of D-type retrovirus capsids. J. Virol. 61: 1045-1053.
117. Rice, W. G., D. C. Baker, C. A. Schaeffer, L. Graham, M. Bu, S. Terpening, D. Clanton, R. Schultz, J. P. Bader, R. W. Buckheit, Jr., L. Field, P. K. Singh, and J. A. Turpin. 1997. Inhibition of multiple phases of human immunodeficiency virus type 1 replication by a dithiane compound that attacks the conserved zinc fingers of retroviral nucleocapsid proteins. Antimicrob. Agents Chemother. 41:419-426.
118. Rice, W. G., C. A. Schaeffer, B. Harten, F. Villinger, T. L. South, M. F. Summers, L. E. Henderson, J. W. Bess, Jr., L. O. Arthur, J. S. McDougal, et al. 1993. Inhibition of HIV-1 infectivity by zinc-ejecting aromatic C-nitroso compounds. Nature 361:473-475.
119. Rice, W. G., J. G. Supko, L. Malspeis, R. W. Buckheit, Jr., D. Clanton, M. Bu, L. Graham, C. A. Schaeffer, J. A. Turpin, J. Domagala, et al. 1995 Inhibitors of HIV nucleocapsid protein zinc fingers as candidates for the treatment of AIDS. Science 270:1194-1197.
120. Rice, W. G., J. A. Turpin, C. A. Schaeffer, L. Graham, D. Clanton, R. W. Buckheit, Jr., D. Zaharevitz, M. F. Summers, A. Wallqvist, and D. G. Covell. 1996. Evaluation of selected chemotypes in coupled cellular and molecular target-based screens identifies novel HIV-1 zinc finger inhibitors. J. Med. Chem. 39:3606-3616.
121. Roberts, N. A., J. A. Martin, D. Kinchington, A. V. Broadhurst, J. C. Craig. I. B. Duncan, S, A. Galpin, B. K. Handa, J. Kay, A. Krohn, et al. 1990. Rational design of peptide-based HIV proteinase inhibitors. Science 248: 358-361.
122. Rose, J. R., L. M. Babe, and C. S. Craik. 1995. Defining the level of human immunodeficiency virus type 1 (HIV-1) protease activity required for HIV-1 particle maturation and infectivity. J. Virol. 69:2751-2758.
123. Rose, J. R., R. Salto, and C. S. Craik. 1993. Regulation of autoproteolysis of the HIV-1 and HIV-2 proteases with engineered amino acid substitutions. J. Biol. Chem. 268:11939-11945.
124. Saltarelli, M. J., E. Hadziyannis, C. E. Hart, J. V. Harrison, B. K. Felber, T. J. Spira, and G. N. Pavlakis. 1996. Analysis of human immunodeficiency virus type 1 mRNA splicing patterns during disease progression in peripheral blood mononuclear cells from infected individuals. AIDS Res. Hum. Retrovir. 12:1443-1456.
125. Schapiro, J. M., M. A. Winters, F. Stewart, B. Efron, J. Norris, M. J. Kozal, and T. C. Merigan. 1996. The effect of high-dose saquinavir on viral load and CD4+ T-cell counts in HIV-infected patients. Ann. Intern. Med. 124: 1039-1050.
126. Schneider, R., M. Campbell, G. Nasioulas, B. K. Felber, and G. N. Pavlakis. 1997. Inactivation of the human immunodeficiency virus type 1 inhibitory elements allows Rev-independent expression of Gag and Gag/protease and particle formation. J. Virol. 71:4892-4903.
127. Schwartz, S., B. K. Felber, D. M. Benko, E. M. Fenyo, and G. N. Pavlakis, 1990. Cloning and functional analysis of multiply spliced mRNA species of human immunodeficiency virus type 1. J. Virol. 64:2519-2529.
128. Sei, S., H. Akiyoshi, J. Bernard, D. J. Venzon, C. H. Fox, D. J. Schwartzentruber, B. D. Anderson, J. B. Kopp, B. U. Mueller, and P. A. Pizzo. 1996. Dynamics of virus versus host interaction in children with human immunodeficiency virus type 1 infection. J. Infect. Dis. 173:1485-1490.
129. Sei, S., D. E. Kleiner, J. B. Kopp, R. Chandra, P. E. Klotman, R. Yarchoan, P. A. Pizzo, and H. Mitsuya. 1994. Quantitative analysis of viral burden in tissues from adults and children with symptomatic human immunodeficiency virus type 1 infection assessed by polymerase chain reaction. J. Infect. Dis. 170:325-333.
130. Shirasaka, T., M. F. Kavlick, T. Ueno, W. Y. Gao, E. Kojima, M. L. Alcaide, S. Chokekijchai, B. M. Roy, E. Arnold, R. Yarchoan, et al. 1995. Emergence of human immunodeficiency virus type 1 variants with resistance to multiple dideoxynucleosides in patients receiving therapy with dideoxynucleosides. Proc. Natl. Acad. Sci. USA 92:2398-2402.
131. Shoji, Y., S. Akhtar, A. Periasamy, B. Herman, and R. L. Juliano. 1991. Mechanism of cellular uptake of modified oligodeoxynucleotides containing methylphosphonate linkages. Nucleic Acids Res. 19:5543-5550.
132. Simmons, G., P, R. Clapham, L. Picard, R. E. Offord, M. M. Rosenkilde, T. W. Schwartz, R. Buser, T. N. C. Wells, and A. E. Proudfoot. 1997. Potent inhibition of HIV-1 infectivity in macrophages and lymphocytes by a novel CCR5 antagonist. Science 276:276-279.
133. gag-pol from human immunodeficiency virus type 1 into virus-like particles. J. Virol. 67:2266-2275.
134. Srinivasakumar, N., M. L. Hammarskjold, and D. Rekosh. 1995. Characterization of deletion mutations in the capsid region of human immunodeficiency virus type 1 that affect particle formation and Gag-Pol precursor incorporation. J. Virol. 69:6106-6114.
135. Strickler, J. E., J. Gorniak, B. Dayton, T. Meek, M. Moore, V. Magaard, J. Malinowski, and C. Debouck. 1989. Characterization and autoprocessing of precursor and mature forms of human immunodeficiency virus type 1 (HIV 1) protease purified from Escherichia coli. Proteins 6:139-154.
136. Tanaka, M., R. V. Srinivas, T. Ueno, M. F. Kavlick, F. K. Hui, A. Fridland, J. S. Driscoll, and H. Mitsuya. 1997. In vitro induction of human immunodeficiency virus type 1 variants resistant to 2'-β-fluoro-2',3'-dideoxyadenosine. Antimicrob. Agents Chemother. 41:1313-1318.
137. Turpin, J. A., Y. Song, J. K. Inman, M. Huang, A. Wallqvist, A. Maynard, D. G, Covell, W. G. Rice, and E. Appella. 1999. Synthesis and biological properties of novel pyridinioalkanoyl thiolesters (PATE) as anti-HIV-1 agents that target the viral nucleocapsid protein zinc fingers. J. Med. Chem. 42:67-86.
138. Vickers, T. A., and D. J. Ecker. 1992. Enhancement of ribosomal frameshifting by oligonucleotides targeted to the HIV gag-pol region. Nucleic Acids Res. 20:3945-3953.
139. Walder, R. Y., and J. A. Walder. 1988. Role of RNase H in hybrid-arrested translation by antisense oligonucleotides. Proc. Natl. Acad. Sci. USA 85: 5011-5015.
140. Wang, S., and B. J. Dolnick. 1993. Quantitative evaluation of intracellular sense: antisense RNA hybrid duplexes. Nucleic Acids Res. 21:4383-4391.
141. Weichold, F. F., J. Lisziewicz, R. A. Zeman, L. S. Nerurkar, S. Agrawal, M. S. Reitz, Jr., and R. C. Gallo. 1995. Antisense phosphorothioate oligodeoxynucleotides alter HIV type 1 replication in cultured human macrophages and peripheral blood mononuclear cells. AIDS Res. Hum. Retrovir. 11:863-867.
142. Willey, R. L., M. A. Martin, and K. W. Peden. 1994. Increase in soluble CD4 binding to and CD4-induced dissociation of gp120 from virions correlates with infectivity of human immunodeficiency virus type 1. J. Virol. 68:1029-1039.
143. Wilson, W., M. Braddock, S. E. Adams, P. D. Rathjen, S. M. Kingsman, and A. J. Kingsman. 1988. HIV expression strategies: ribosomal frameshifting is directed by a short sequence in both mammalian and yeast systems. Cell 55: 1159-1169.
144. Wittung, P., J. Kajanus, K. Edwards, G. Haaima, P. E. Nielsen, B. Norden, and B. G. Malmstrom. 1995. Phospholipid membrane permeability of peptide nucleic acid. FEBS Lett. 365:27-29. (Correction and republication, 375:27-29.)
145. Wittung, P., P. E. Nielsen, O. Buchardt, M. Egholm, and B. Norden. 1994. DNA-like double helix formed by peptide nucleic acid. Nature 368:561-563.
146. Wlodawer, A., M. Miller, M. Jaskolski, B. K. Sathyanarayana, E. Baldwin, I. T. Weber, L. M. Selk, L Clawson, J. Schneider, and S. B. Kent. 1989. Conserved folding in retroviral proteases: crystal structure of a synthetic HIV-1 protease. Science 245:616-621.
147. Wong, J. K., M. Hezareh, H. F. Günthard, D. V. Havlir, C. C. Ignacio, C. A. Spina, and D. D. Richman. 1997. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science 278:1291-1295.
148. Yamaguchi, K., B. Papp, D. Zhang, A. N. Ali, S. Agrawal, and R. A. Byrn. 1997. The multiple inhibitory mechanisms of GEM 91, a gag antisense phosphorothioate oligonucleotide, for human immunodeficiency virus type 1. AIDS Res. Hum. Retrovir. 13:545-554.
149. Yarchoan, R., R. W. Klecker, K. J. Weinhold, P. D. Markham, H. K. Lyerly, D. T. Durack, E. Gelmann, S. N. Lehrman, R. M. Blum, D. W. Barry, et al. 1986. Administration of 3'-azido-3'-deoxythymidine, an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex. Lancet 1:575-580.
150. Yarchoan, R., H. Mitsuya, R. V. Thomas, J. M. Pluda, N. R. Hartman, C. F. Perno. K. S. Marczyk, J. P. Allain, D. G. Johns, and S. Broder. 1989. In vivo activity against HIV and favorable toxicity profile of 2',3'-dideoxyinosine. Science 245:412-415.
151. Yoshimura, K., R. Kato, K. Yusa, M. F. Kavlick, V. Maroun, A. Nguyen, T. Mimoto, T. Ueno, M. Shintani, J. Falloon, H. Masur, H. Hayashi, J. Erickson, and H. Mitsuya. 1999. JE-2147: a dipeptide protease inhibitor (PI) that potently inhibits multi-PI-resistant HIV-1. Proc. Natl. Acad. Sci. USA 96: 8675-8680.
152. gag domain result in reduced retention of Pol proteins during virus assembly. J. Virol. 72: 3412-3417.
153. Zhang, L., B. Ramratnam, K. Tenner-Racz, Y. He, M. Vesanen, S. Lewin, A. Talal, P. Racz, A. S. Perelson, B. T. Korber, M. Markowitz, and D. D. Ho. 1999. Quantifying residual HIV-1 replication in patients receiving combination antitetroviral therapy. N. Engl. J. Med. 340:1605-1613.
154. Zhao, H., N. Neamati, H. Hong, A. Mazumder, S. Wang, S. Sunder, G. W. Milne, Y. Pommier, and T. R. Burke, Jr. 1997 Coumarin-based inhibitors of HIV integrase. J. Med. Chem. 40:242-249.
155. Zhao, H., N. Neamati, S. Sunder, H. Hong, S. Wang, G. W. Milne, Y. Pommier, and T. R, Burke, Jr. 1997. Hydrazide-containing inhibitors of HIV-1 integrase. J. Med. Chem. 40:937-941.