Oncogene Science, Inc., 106 Charles Lindbergh Blvd., Uniondale, NY 11553

Received 6/2/97; Accepted 6/4/97

7. References

1. Cullen, B. R. Regulation of human immunodeficiency virus replication.Annu. Rev. Microbiol. 45, 219-250 (1991)

2. Haseltine, W. A. Molecular biology of the human immunodeficiency virus type 1. FASEB 5, 2349-2360 (1991)

3. Vaishnav, Y. N. and Wong-Staal, F. The biochemistry of AIDS. Annu. Rev. Biochem. 60, 577-630 (1991)

4. Cullen, B. R. and Malim, M. H. The HIV1 Rev protein: prototype of a novel class of eukaryotic posttranscriptional regulators.TIBS 16, 346-350 (1991).

5. Malim, M. H., Hauber, J., Fenrick, R. and Cullen, B. R. Immunodeficiency virus rev transactivator modulates the expression of the viral regulatory genes. Nature 335, 181-183 (1988).

6. Emerman, M., Vazeux, R. and Peden, K. The rev gene product of the human immunodeficiency virus affects envelopespecific RNA localization. Cell 57, 1155-1165 (1989).

7. Hadzopoulou-Cladaras, M., Felber, B. K., Cladaras, C., Athanassopoulus, A., Tse, A. and Pavlakis, G. The rev (trs/art) protein of human immunodeficiency virus type 1 affects viral mRNA and protein expression via a cisacting sequence in the env region. J. Virol. 63, 1265-1274 (1989).

8. Rosen, C., Terwilliger, E., Dayton, A., Sodroski, J. and Haseltine, W. Intragenic cisacting art generesponsive sequences of the human immunodeficiency virus. Proc.Natl. Acad. Sci. USA 85, 2071-2075 .

9. Zapp, M. L. and Green, M. R. Sequence-specific RNA binding by the HIV-1 Rev protein. Nature 342, 714-716 (1989).

10. Olsen, H. S., Nelbock, P., Cochrane, A. W. and Rosen, C. A. Seconary structure is the major determinant for interaction of HIV rev protein with RNA. Science 247, 845-848 (1990).

11. Cochrane, A. W., Chen, C. H. and Rosen, C. A. Specific interaction of the human immunodeficiency virus Rev protein with a structured region in the env mRNA. Proc. Natl. Acad. Sci. USA 87, 1198-1202 (1990).

12. Malim, M. H., Bohnlein, S., Hauber, J. and Cullen, B. R. Functional dissection of the HIV1 Rev transactivatorderivation of a transdominant repressor of Rev function. Cell 58, 205-214 (1989).

13. Malim, M. H. and Cullen, B. R. HIV1 structural gene expression requires the binding of multiple Rev monomers to the viral RRE: implications for HIV1 latency. Cell 65, 241-248 (1991).

14. Kjems, J., Calnan, B. J., Frankel, A. D. and Sharp, P. A. Specific binding of a basic peptide from HIV1 Rev. EMBO J. 11, 1119-1129 (1992).

15. Tan, R., Chen, L., Buettner, J.A., Hudson, D., and Frankel, A.D. RNA recognition by an isolated alpha helix. Cell 73, 1031-1040 (1993).

16. Olsen, H. S., Cochrane, A. W., Dillon, P. J., Nalin, C. M. and Rosen, C. A. Interaction of the human immunodeficiency virus type 1 Rev protein with a structured region in env mRNA is dependent on multimer formation mediated through a basic stretch of amino acids. Genes Dev. 4, 1357-1364 (1990b).

17. Zapp, M. L., Hope, T. J., Parslow, T. G. and Green, M. R. Oligomerization and RNA binding domains of the type 1 human immunodeficiency virus Rev protein: a dual function for an arginine-rich binding motif. Proc. Natl. Acad.Sci.USA 88, 7734-7738 (1991).

18. Madore, S. J., Tiley, L. S., Malim, M.H. and Cullen B. R. Sequence requirements for Rev multimerization in vivo. Virology 202,186-194 (1994).

19. Cook, K.S., Fisk, G. J., Hauber, J., Usman, N., Daly, T.J. and Rusche, J. R. Characterization of HIV-1 REV protein: binding stoichimetry and minimal RNA substrate. Nucleic Acids Res 19, 1577-1583 (1991).

20. Heaphy, S., Finch, J. T., Gait, M.J., Karn, J. and Singh, M. Human immunodeficiency virus type 1 regulator of virion expression, rev, forms nucleoprotein filaments after binding to a purine-rich "bubble" located within the rev-responsive region of viral mRNAs. Proc. Natl. Acad. Sci. USA 88, 7366-7370 (1991).

21. Bogerd, H. P. and Greene, W. C. Dominant negative mutants of human T-cell leukemia virus type I Rex and human immunodeficiency virus type 1 Rev fail to multimerize in vivo. J. Virol. 67, 2496-2502 (1993).

22. Mermer, B., Felber, B. K., Campbell, M. and Pavlakis, G. N. Identification of trans-dominant HIV-1 rev protein mutatns by direct transfer of bacterially produced protein into human cells. Nucleic Acids Res. 18, 2037-2044 (1990).

23. Venkatesh, L.K., and Chinnadurai, G. Mutants in a converved region near the carboxy-terminus of HIV-1 Rev identify functionally important residues and exhibit a dominant negative phenotype. Virology 178, 327-330 (1990).

24. Hope, T. J. , Bond, B. L., McDonald, D., Klein, N. P. and Parslow, T. Effector domains of human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type 1 Rex are functionally interchangeable and share an essential peptide motif. J. Virol. 65, 6001-6007 (1991).

25. Malim, M. H., McCarn, D. F., Tiley, L. and Cullen, B. R. Mutational definition of the human immunodeficiency virus type 1 Rev activation domain. J. Virol. 65, 4248-4254 (1991).

26. Weischelbraun, I., Farrington, G. K., Rusche, J. R., Boehnlein, E. and Hauber, J. Definition of the human immunodeficiency virus type Rev and human T-cell leukemia virus type I Rex protein activation domain by functional exchange. J. Virol. 66, 2583-2587 (1992).

27. Fischer, U., Huber, J., Boelens, W.C., Mattaj, I.W. and Lührmann, R. The HIV 1 Rev activation domains is a nuclear export signal that accesses an export pathway used by specific cellular RNAs. Cell 82, 475-483 (1995).

28. Wen, W., Meinkoth, J.L., Tsien, R.Y. and Taylor, S.S. Identification of a signal for rapid export of proteins from the nucleus. Cell 82, 463-473 (1995).

29. Fridell, R.A., Bogerd, H. P. and Cullen, B. R. Nuclear export of late HIV1 mRNAs occurs via a cellular protein export pathway. Proc. Natl. Acad. Sci. USA 93, 4421-4424 (1996).

30. Meyer, B.E., Meinkoth, J.L. and Malim, M.H. Nuclear transport of human immunodeficiency virus type 1, visna virus, and equine infectious anemia virus Rev protein: identification of a family of transferable nuclear export signals. J. Virol. 70, 2350-2359 (1996).

31. Fridell, R.A., Benson, R.E., Hua, J., Bogerd, H.P. and Cullen, B.R. A nuclear role for the Fragile X mental retardation protein. EMBO J. 15, 5408-5414 (1996).

32. Fridell, R.A., Fischer, U., Lührmann, R., Meyer, B.E., Meinkoth, J.L., Malim, M.H., and Cullen, B. R. Amphibian transcription factor IIIA proteins contain a sequence element functionally equivalent to the nuclear export signal of human immunodeficiency virus type 1 Rev. Proc. Natl. Acad. Sci. USA 93, 2936-2940 (1996).

33. Dayton, E. T., Powell, D. M. and Dayton, A. I. Functional analysis of CAR, the target sequence for the Rev protein of HIV-1. Science 246, 1625-1629 (1989).

34. Heaphy, S., Dingwall, C., Ernberg, I., Gait, M. J., Green, S. M., Karn, J., Lowe, A. D., Singh, M. and Skinner, M. A. HIV-1 regulator of virion expression (Rev) protein binds to an RNA stem-loop structure located within the Rev response element region. Cell 60, 685-693 (1990).

35. Malim, M. H., Tiley, L. S., McCarn, D. F., Rusche, J. R., Hauber, J. and Cullen, B.R. HIV1 structural gene expression requires binding of the Rev transactivator to its RNA target sequence. Cell 60, 675-683 (1990).

36. Tiley, L.S., Malim, M.H., Tewary, H.K., Stockley, P.G and Cullen, B.R. Identification of a highaffinity RNAbinding site for the human immunodeficiency virus type 1 Rev protein. Proc. Natl. Acad. Sci. USA 89, 758-762 (1992).

37. Bartel, D.P., Zapp, M.L., , Green, M.R. and Szostak, J.W. HIV-1 Rev regulation involves recognition of non-Watson-Crick base pairs in viral RNA. Cell 67, 529-536 (1991).

38. Giver, L., Bartel, D.P., Zapp, M.L. and Ellington, D.A. Selection and design of high-affinity RNA ligands for HIV-1 Rev. Gene 137, 19-24 (1993).

39. Leclerc, F., Cedegren, R. and Ellington, A.D. A three-dimensional model of the Rev-binding element of HIV-1 derived from analyses of aptamers. Nature Struct. Biol. 1, 293-300 (1994).

40. Werstruck, G., Zapp, M.L. and Green, M.R. A non-canonical base pair withint the human immunodeficiency virus rev-responsive element is involved in both rev and small molecule recognition. Chem. Biol. 3, 129-137 (1996).

41. Battiste, J.L., Tan, R., Frankel, A.D. and Williamson, J.R. Assignment and modeling of the Rev response element RNA bound to a Rev peptide using 13C-heteronuclear NMR. J. Biomol. Nucl. Magn. Reson. 6, 375-389 (1995).

42. Iwai, S., Pritchard, C., Mann, D.A., Karn, J. and Gait, M.J. Recognition of the high affinity binding site in rev-response element RNA by the human immunodeficiency virus type-1 rev protein. Nucl. Acids. Res. 20, 6465-6472 (1992).

43. Jain, C. and Belasco, J.G. A structural model for the HIV-1 Rev-RRE complex deduced from altered-specificity rev variants isolated by a rapid genetic strategy. Cell 87, 115-125 (1996).

44. Ye, X., Gorin, A., Ellington, A.D. and Patel, D.J. Deep penetration of an alpha-helix into a widened RNA major groove in the HIV-1 rev peptide-RNA aptamer complex. Nature Struct. Biol. 3, 1026-1033 (1996).

45. Battiste, J.L., Mao, H., Rao, N.S., Tan, R., Muhandiram, D.R., Kay, L.E., Frankel, A.D. and Williamson, J.R. Alpha helix-RNA major groove recognition in an HIV-1 rev peptide-RRE RNA complex. Science 273, 1547-1551 (1996).

46. Grate, D. and Wilson, C. Role REVersal: understanding how RRE RNA binds its peptide ligand. Structure 5 7-11 (1997).

47. Ivey-Hoyle, M. and Rosenberg, M Rev-dependent expression of human immunodeficiency virus type 1 gpl60 in Drosophila melanogaster cells. Mol. Cell. Biol. 10, 6152-6159 (1990).

48. Fischer, U., Meyer, S., Teufel, M., Heckel, C., Lührmann, R. and Rautmann, G. Evidence that HIV-1 Rev directly promotes the nuclear export of unspliced RNA. EMBO J. 13, 4105-4112 (1994).

49. Stutz, F. and Rosbash, M. A functional interaction between Rev and yeast pre-mRNA is related to splicing complex formation. EMBO J. 13, 4096-4104 (1994).

50. Luo, Y., Yu, H. and Peterlin, B.M. Cellular protein modulates effects of human immunodeficiency virus type 1 Rev. J.Virol. 68, 3850-3856 (1994).

51. Tange, T.O., Jensen, T.H. and Kjems, J. In vitro interaction between human immunodeficiency virus type 1 Rev protein and splicing factor ASF/SF2-associated protein, p32. J. Biol. Chem. 271, 10066-10072 (1996).

52. Powell, D.M., Amaral, M.C., Yu, J.Y., Maniatis, T. and Greene, W.C. HIV Rev-dependent binding of SF2/ASF to the Rev response element: possible role in Rev-mediated inhibition of HIV RNA splicing. Proc. Natl. Acad. Sci. USA 94, 973-978 (1997).

53. Krainer, A.R., Mayeda, A., Kozak, D. and Binns, G. Functional expression of cloned human splicing factor SF2, homology to RNA-binding proteins, U1 70K, and Drosophila splicing regulators. Cell 66, 383-394 (1991).

54. Fridell, R.A., Harding, L.S., Bogerd, H.P. and Cullen, B.R. Identification of a novel human zinc finger protein that specifically interacts with the activation domain of lentiviral Tat proteins. Virology 209, 347-357 (1995).

55. McDonald, D., Hope, T.J. and Parslow, T.G. Posttranscriptional regulation by the human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex proteins through a heterologous RNA binding site. J. Virol. 66, 7232-7238 (1992).

56. Ruhl, M., Himmelspach, M., Bahr, G. M., Hammerschmid, F., Jaksche, H., Wolff, B., Aschauer, H., Farrington, G. K., Probst, H., Bevec, D. and Hauber, J. Eukaryotic initiation factor 5A is a cellular target of the human immunodeficiency virus type 1 Rev activation domain mediating trans-activaton. J. Cell Biol. 123, 1309-1320 (1993).

57. Fritz, C.C., Zapp, M.L. and Green, M.R. A human nucleoporin-like protein that specifically interacts with HIV Rev. Nature 376, 530-533 (1995).

58. Bogerd, H. P., Fridell, R. A., Madore, S. and Cullen, B. R. Identification of a novel cellular cofactor for the Rev/Rex class of retroviral regulatory proteins. Cell 82, 485-494 (1995).

59. Stutz, F., Neville, M. and Rosbash, M. Identification of a novel nuclear pore-associated protein as a functional target of the HIV-1 Rev protein in yeast. Cell 82, 495-506 (1995).

60. Stutz, F., Izaurralde, E., Mattaj, I.W. and Rosbash, M. A role for nucleoporin FG repeat domains in export of human immunodeficiency virus type 1 Rev protein and RNA from the nucleus. Mol. Cell. Biol. 16, 7144-7150 (1996).

61. Bevec, D., Jaksche, H., Oft, M., Wöhl, T., Himmelspach, M., Pacher, A., Schebesta, M., Koettnitz, K., Dobrovnik, M., Csonga, R., Lottspeich, F. Hauber, J. Inhibition of HIV-1 replication in lymphocytes by mutants of the Rev cofactor eIF-5A. Science 271, 1858-1860 (1996).

62. Rout, M.P. and Wente, S. R. Trends Cell Biol. 4, 357-365 (1994).

63. Chang, D.D. and Sharp, P.A. Regulation by HIV Rev depends upon recognition of splice sites. Cell 59, 789-795 (1989).

64. Kjems, J., Frankel, A. D. and Sharp, P. A. Specific regulation of mRNA splicing in vitro by a peptide from HIV-1 Rev. Cell 67, 169-178 (1991).

65. Kjems, J. and Sharp. P.A. The basic domain of Rev from human immunodeficiency virus type 1 specifically blocks the netry of U4/U6.U5 small nuclear ribonucleoprotein in spliceosome assembly. J. Virol. 67, 4769-4776 (1993).

66. Malim, M. H. and Cullen, B. R. Identification of a novel cellular cofactor for the Rev/Rex class of retroviral regulatory proteins. Mol. Cell. Biol. 13, 6180-6189 (1993).

67. Bray, M., Prasad, S., Dubay, J. W., Hunter, E., Jeang, K.-T., Rekosh, D. and Hammarskjold, M.-L. A small element from the Mason-Pfizer monkey virus genome makes human immunodeficiency virus type 1 expression and replication Rev-independent. Proc. Nat. Acad. Sci. USA 91, 1256-1260 (1994).

68. Bridges, S.H. and Sarver, N. Gene therapy and immuno restoration for HIV disease. The Lancet 345, 427-432 (1995).

69. Yu, M., Poeschla, E., and Wong-Staal, F. Progress towards gene therapy for HIV infection. Gene Ther. 1, 13-26 (1994).

70. Dropulic, B. and Jeang, K.-T. Gene therapy for human immunodeficiency virus infection: genetic antiviral strategies and targets for intervention. Hum. Gene Ther. 5, 927-939 (1994).

71. Lever, A.M.L. Gene therapy for HIV infection. Brit. Med. Bull. 51, 149-166 (1995).

72. Stauber, R., Gaitinaris, G. A., and Pavlakis, G. N. Analysis of trafficking of Rev and transdominant Rev proteins in living cells using green fluorescent protein fusions: transdominant Rev blocks the export of Rev from the nucleus to the cytoplasm. Virology 213, 439-449 (1995).

73. Malim, M.H., Freimuth, W.W., Liu, J., Boyle, T.J., Lyerle, H.K., Cullen, B.R. and Nabel, G.J. Identification of a novel cellular cofactor for the Rev/Rex class of retroviral regulatory proteins. J. Exp. Med. 176, 1197-1201 (1992).

74. Bevec, D., Dobrovnik, M., Hauber, J. and Böhnlein, E. Inhibition of human immunodeficiency virus type 1 replication in human T cells by retroviral-mediated gene transfer of a dominant-negative Rev trans-activator. Proc. Natl. Acad. Sci. USA 89, 9870-9874 (1992).

75. Bahner, I, Zhou, C., Yu, X.-J., Hao, Q.-L., Guatelli, J. C. and Kohn, D.B. Comparison of trans-dominant inhibitory mutant human immuodeficiency virus type 1 genes expressed in retroviral vectors in human T lymphocytes. J. Virol. 67, 3199-3207 (1993).

76. Escaich, S., Kalfoglou, C., Plavec, I, Kaushal, S., Mosca, J.D. and Böhnlein, E. Hum. Gene Ther. 6, 625-634 (1995).

77. Woffendin, C., Ranga, U., Yang, Z.-Y., Xu, L. and Nabel, G.J. Expression of a protective gene-prolongs survival of T cells in human immunodeficiency virus-infected patients. Proc. Natl. Acad. Sci. USA 93, 2889-2894 (1996).

78. Plavec, I., Agarwal, M., Ho, K.E., Pineda, M., Auten, J., Baker, J., Matsuzaki, H., Escaich, S., Bonyhadi, M. and Böhnlein, E. High transdominant RevM10 protein levels are required to inhibit HIV-1 replication in cell lines and primary T cells: implication for gene therapy of AIDS. Gene Ther. 4, 128-139 (1997).

79. Duan, L., Bagasra, O., Laughlin, M.A., Oakes, J.W. and Pomerantz, R.J. Potent inhibitor of human immunodeficiency virus type 1 replication by an intracellular anti-Rev single-chain antibody. Proc. Natl. Acad. Sci. USA 91, 5075-5079 (1994).

80. Cech, T.R., Bass, B.L. Biological catalysis by RNA. Annu. Rev. Biochem. 55, 599-629 (1986).

81. Sarver, N., Cantin, E.M., Chang, P.S., Zaia, J. A., Ladne, P.A., Stephens, D.A. and Rossi, J.J. Ribozymes as potential anti-HIV-1 therapeutic agents. Science 247, 1222-1225 (1990).

82. Weerasinghe, M., Liem, S.E., Asad, S., Read, S.E. and Joshi, S. Resistance to human immunodeficiency virus type (HIV-1) infection in human CD4+ lymphocyte-derived cell lines conferred by using retroviral vectors expressing an HIV-1 RNA-specific ribozyme. J. Virol. 65, 5531-5534 (1991).

83. Dropulic, B., Lin, N.H., Martin, M.A. and Jeang, K.-T. Functional characterization of a U5 ribozyme: intracellular suppression of human immunodeficiency virus type 1 expression. J. Virol. 66, 1432-1441 (1992).

84. Zhou, C., Bahner, I, Larson, G., Zaia, J.A., Rossi, J. J. and Kohn, D.B. Inhibition of HIV-1 in human T-lymphocytes by retrovirally transduced anti-tat and rev hammerhead ribozymes. Gene 149, 33-39 (1994).

85. Yamada, O., Kraus, G., Luznik, L., Yu, M. and Wong-Staal, F. A chineric human immunodeficiency virus type 1 (HIV-1) minimal Rev response element-ribozyme molecular exhibits dual antiviral function and inhibits cell-cell transmission of HIV-1. J. Virol. 70, 1596-1601 (1996).

86. Gervaix, A., Li, X., Kraus, G. and Wong-Staal, F. Multigene antiviral vectors inhibit diverse human immunodeficiency virus type 1 clades. J. Virol. 71, 3048-3053 (1997).

87. Graham, G.J. and Maio, J.J. RNA transcripts of the human immunodeficiency virus transactivation response element can inhibit action of the viral transactivator. Proc. Natl. Acad. Sci. USA 87, 5817-5821 (1990).

88. Lee, T.C., Sullenger, B.A., Gallardo, H.F., Ungers, G.E. and Gilboa, E. Overexpression of RRE-derived sequences inhibits HIV-1 replication in CEM cells. New Biol. 4, 66-74 (1992).

89. Kim, J.H., McLinden, R.J., Mosca, J.D., Vahey, M.T., Greene, W.C. and Redfield, R.R. Inhibition of HIV replication by sense and antisense rev response elements in HIV-based retroviral vectors. J. Acquir. Immun. Defic. Syndr. Hum. Retrovir. 12, 343-351 (1996).

90. Rhodes, A. and James, W. Inhibition of human immunodeficiency virus replication in cell culture by endogenously synthesized antisense RNA. J. Gen. Virol. 71, 1965-1974 (1990).

91. Rhodes, A. and James, W. Inhibition of heterologous strains of HIV by antisense RNA. AIDS 5, 145-151 (1991).

92. Green, P.J., Pines, O. and Inouye, M. The role of antisense RNA in gene regulation. Annu. Rev. Biochem. 55, 569-597 (1986).

93. Stein, C.A. and Cheng, Y.C. Antisense oligonucleotides as therapeutic agents - is the bullet really magical? Science 261, 1004-1012 (1993).

94. Matsukara, M., Zon, G., Shinozuka, M., Robert-Guroff, T., Shimable, C., Stein, H., Mitsuya, H., Wong-Staal, F., Cohen, J.S. and Broder, S. 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 (1989).

95. Chin, D.J. Inhibition of human immunodeficiency virus type 1 rev-rev-response element complex formation by complementary oligonucleotides. J. Virol. 66, 600-607 (1992).

96. Li, G., Lisziewicz, Sun, D., Zon, G., Daefler, S., Wong-Staal, F., Gallo, R.C. and Klotman, M.E. Inhibition of Rev activity and human immunodeficiency virus type 1 replication by antisense oligdeoxynycleotide phosphorothioate analogs directed against the Rev-responsive element. J. Virol. 6882-6888 (1993).

97. Fenster, S.D., Wagner, R.W., Froehler, B.C. and Chin, D.J. Inhibition of human immunodeficiency virus type-1 env expression by C-5 propyne oligonucleotides specific for Rev-response element stem-loop V. Biochemistry 33, 8391-8398 (1994).

98. Nakaya, T., Iwai, S., Fujinaga, K., Sato, Y., Otsuka, E. and Ikuta, K. Decoy approach using RNA-DNA chimera oligonucleotides to inhibit the regulatory function of human immunodeficiency virus type 1 Rev protein. Antimicrob. Agents Chemother. 41, 319-325 (1997)

99. Schroder, H.C., Ushijima, H., Bek, A., Merz, H., Pfeifer, P., Muller, W. E. G. Inhibition of formation of Rev-RRE complex by pyronin Y. Antiviral Chem. Chemother 4, 103-109 (1993).

100. Ratmeyer, L., Zapp, M.L., green, M.R., Vinayak, R., Kumar, A., Boykin, D.W. and Wilson, W.D. Inhibition of HIV-1 Rev-RRE interaction by diphenylfuran derivatives. Biochemistry 35, 13689-13696 (1996).

101. Zapp, M. L., Stern, S. and Green, M. R. Small molecules that selectively block RNA binding of HIV-1 Rev protein inhibit Rev function and viral production. Cell 74, 969-978 (1993).

102. Woodcock, J., Moazed, D., Cannon, M., Davis, J. and Noller, H. F. Interaction of antibiotics with A- and P-site-specific bases in 16S ribosomal RNA. EMBO J. 10, 3099-3103 (1991).

103. Purohit, P., and Stern, S. Interactions of a small RNA with antibiotic and RNA ligands of the 30S subunit. Nature 370, 659-662 (1994).

104. von Ahsen, U., Davis, J., and Schroeder, R. Antibiotic inhibition of group I ribozyme function. Nature 353, 368-370 (1991).

105. Stage, T.K., Hertel, K.J. and Uhlenbeck, O.C. Inhibition of the hammerhead ribozyme by neomycin. RNA 1, 95-101 (1995).

106. Wang, Y., Hamasaki, K. and Rando, R.R. Specificity of aminoglycoside binding to RNA constructs from the 16S rRNA decoding region and the HIV-RRE activator region. Biochemistry 36, 768-779 (1997).

107. Chambers, H.F. and Sanders, M.A. Antimicrobial agents: the aminoglycosides . In Goodman & Gilman's The Pharmacological Basis of Therapeutics. Eds.: Hardman, J. G., Limbird, L.E., Molinoff, P.B., Ruddon, R.W. and Gilman, A.G. McGraw-Hill, NY (1996).

108. Ciccarelli, R. B.; Winter, L. A., Lorenz, R., Harris, A., Crawford, a. C., Bailey, T. R., Singh, B., Hammarskjold, M.-L., Rekosh, D. and Hughes, J. V. Inhibition of the cellular Rex response and HIV-1 replication by 8-Alkyl-2-(4-pyridyl)pyrido[2,3-d] pyrimidin-5(8H)-ones. Antiviral Chem. Chemother. 5, 169-175 (1994).

109. Qian-Cutrone, J., Huang, S., Trimble, J., Li, H., Lin, P.-F., Alam, M., Klohr, S. E. and Kadow, K.F. Niruriside, a new HIV REV/RRE binding inhibitor from Phyllanthus niruri. J. Nat. Prod. 59, 196-199 (1996).

110. Qian-Cutrone, J., Huang, S., Chang, L.-P., Pirnik, D.M., Klohr, S.E., Dalterio, R.A., Hugill, R., Lowe, S., Alam, M. and Kadow, K.F. Harziphilone and fleephilone, two new HIV REV/RRE binding inhibitors produced by Trichoderma harzianum. J. Antibiotics 49, 990-997 (1996).

111. Wolff, B., Sanglier, J.-J. and Wang, J. Leptomycin B is an inhibitor of nuclear export: inhibition of nucleo-cytoplasmic translocation of the human immunodeficiency virus type 1 (HIV-1) Rev protein and Rev-dependent mRNA. Chem. Biol. 4, 139-147 (1997).