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Prospects for Gene Therapy Using HIV-Based Vectors

  • Published:
Somatic Cell and Molecular Genetics

Abstract

Recombinant vectors derived from murine leukemia virus (MLV) have been widely used to introduce genes in human gene therapy clinical trials and have shown the potential for medical applications and the promise of significantly improving medical therapies. Yet, the demonstrated limitations of these vectors support the need for continued development of improved vectors. The intrinsic properties associated with the MLV genome and its life cycle do not favor the successful application of this vector system in certain human gene transfer applications. Since MLV integrates randomly into the host genome, transgene expression is frequently affected by the flanking host chromatin.1 MLV insertions can often result in silencing or position effect variation of gene expression either immediately after insertion or following cell expansion in culture or in vivo.2–6 Migration of the MLV pre-integration complex from the cytoplasm into the nucleus of infected cells requires mitosis for nuclear membrane breakdown.7 Since a majority of human cells exist in a quiescent state in vivo, it is unlikely that direct in vivo gene delivery into target tissues can be achieved with the MLV vector system. Finally, insertion of tissue-specific cis-regulatory sequences to direct transgene expression frequently results in either the rearrangement of the vector sequence or disruption of the cis-regulatory sequence functions.8–12 The long terminal repeat (LTR) of MLV, which contains a ubiquitously active enhancer/promoter element, may partially account for this problem. Together, these problems pose a major obstacle for the use of MLV vectors in the treatment of human diseases. This Chapter discusses some of the potential targets to which HIV vectors might be applied in clinical settings and some of the issues surrounding use of HIV vectors in gene transfer clinical trials.

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References

  1. Hoeben RC, Migchielsen AA, van der Jagt RC et al. Inactivation of the Moloney murine leukemia virus long terminal repeat in murine fibroblast cell lines is associated with methylation and dependent on its chromosomal position. J Virol 1991; 65(2):904-912.

    Google Scholar 

  2. Flanagan JR, Becker KG, Ennist DL et al. Cloning of a negative transcription factor that binds to the upstream conserved region of Moloney murine leukemia virus. Mol Cell Biol 1992; 12(1):38-44.

    Google Scholar 

  3. Palmer TD, Rosman GJ, Osborne WR et al. Genetically modified skin fibroblasts persist long after transplantation but gradually inactivate introduced genes. Proc Natl Acad Sci USA 1991;88(4):1330-1334.

    Google Scholar 

  4. Rivella S, Sadelain M. Genetic treatment of severe hemoglobinopathies: the combat against transgene variegation and transgene silencing. Semin Hematol 1998; 35(2):112-25.

    Google Scholar 

  5. Williams DA, Orkin SH, Mulligan RC. Retrovirus-mediated transfer of human adenosine deaminase gene sequences into cells in culture and into murine hematopoietic cells in vivo. Proc Natl Acad Sci USA 1986; 83(8):2566-2570.

    Google Scholar 

  6. Xu L, Yee JK, Wolff JA et al. Factors affecting long-term stability of Moloney murine leukemia virus-based vectors. Virology 1989; 171(2):331-341.

    Google Scholar 

  7. Roe T, Reynolds TC, Yu G et al. Integration of murine leukemia virus DNA depends on mitosis. Embo J 1993; 12(5):2099-2108.

    Google Scholar 

  8. Chang JC, Liu D, Kan YW. A 36-base-pair core sequence of locus control region enhances retrovirally transferred human beta-globin gene expression. Proc Natl Acad Sci USA 1992;89(7):3107-3110.

    Google Scholar 

  9. Gelinas R, Frazier A, Harris E. A normal level of beta-globin expression in erythroid cells after retroviral cells transfer. Bone Marrow Transplant 1992; 9(Suppl 1):154-157.

    Google Scholar 

  10. Kaptein LC, Breuer M, Valerio D et al. Expression pattern of CD2 locus control region containing retroviral vectors in hemopoietic cells in vitro and in vivo. Gene Ther 1998; 5(3):320-330.

    Google Scholar 

  11. Novak U, Harris EA, Forrester W et al. High-level beta-globin expression after retroviral transfer of locus activation region-containing human beta-globin gene derivatives into murine erythroleukemia cells. Proc Natl Acad Sci USA 1990; 87(9):3386-3390.

    Google Scholar 

  12. Plavec I, Papayannopoulou T, Maury C et al. A human beta-globin gene fused to the human betaglobin locus control region is expressed at high levels in erythroid cells of mice engrafted with retrovirus-transduced hematopoietic stem cells. Blood 1993; 81(5):1384-1392.

    Google Scholar 

  13. Blomer U, Naldini L, Kafri T et al. Highly efficient and sustained gene transfer in adult neurons with a lentivirus vector. J Virol 1997; 71(9):6641-6649.

    Google Scholar 

  14. Kafri T, Blomer U, Peterson DA et al. Sustained expression of genes delivered directly into liver and muscle by lentiviral vectors. Nat Genet 1997; 17(3):314-317.

    Google Scholar 

  15. Miyoshi H, Takahashi M, Gage FH et al. Stable and efficient gene transfer into the retina using an HIV-based lentiviral vector. Proc Natl Acad Sci USA 1997; 94(19):10319-10323.

    Google Scholar 

  16. Naldini L, Blomer U, Gage FH et al. Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Proc Natl Acad Sci USA 1996; 93(21):11382-11388.

    Google Scholar 

  17. Naldini L, Blomer U, Gallay P et al. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 1996; 272(5259):263-267.

    Google Scholar 

  18. Zufferey R, Nagy D, Mandel RJ et al. Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat Biotechnol 1997; 15(9):871-875.

    Google Scholar 

  19. Case SS, Price MA, Jordan CT et al. Stable transduction of quiescent CD34(+)CD38(-) human hematopoietic cells by HIV-1-based lentiviral vectors. Proc Natl Acad Sci USA 1999;96(6):2988-2993.

    Google Scholar 

  20. Miyake K, Suzuki N, Matsuoka H et al. Stable integration of human immunodeficiency virusbased retroviral vectors into the chromosomes of nondividing cells. Hum Gene Ther 1998;9(4):467-475.

    Google Scholar 

  21. Miyoshi H, Smith KA, Mosier DE et al. Transduction of human CD34+ cells that mediate longterm engraftment of NOD/SCID mice by HIV vectors. Science 1999; 283(5402):682-686.

    Google Scholar 

  22. Reiser J, Harmison G, Kluepfel-Stahl S et al. Transduction of nondividing cells using pseudotyped defective high-titer HIV type 1 particles. Proc Natl Acad Sci USA 1996; 93(26):15266-15271.

    Google Scholar 

  23. Sutton RE, Wu HT, Rigg R et al. Human immunodeficiency virus type 1 vectors efficiently transduce human hematopoietic stem cells. J Virol 1998; 72(7):5781-5788.

    Google Scholar 

  24. Uchida N, Sutton RE, Friera AM et al. HIV, but not murine leukemia virus, vectors mediate high efficiency gene transfer into freshly isolated G0/G1 human hematopoietic stem cells. Proc Natl Acad Sci USA 1998; 95(20):11939-11944.

    Google Scholar 

  25. Wang X, Appukuttan B, Ott S et al. Efficient and sustained transgene expression in human corneal cells mediated by a lentiviral vector. Gene Ther 2000; 7(3):196-200.

    Google Scholar 

  26. Bukrinsky MI, Haggerty S, Dempsey MP et al. A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature 1993; 365(6447):666-669.

    Google Scholar 

  27. Gallay P, Hope T, Chin D et al. HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway. Proc Natl Acad Sci USA 1997; 94(18):9825-9830.

    Google Scholar 

  28. Heinzinger NK, Bukinsky MI, Haggerty SA et al. The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells. Proc Natl Acad Sci USA 1994; 91(15):7311-7315.

    Google Scholar 

  29. Kowolik CM, Hu J, Yee JK. Locus Control Region of the Human CD2 Gene in a Lentivirus Vector Confers Position-Independent Transgene Expression. J Virol 2001; 75(10):4641-4648.

    Google Scholar 

  30. May C, Rivella S, Callegari J et al. Therapeutic haemoglobin synthesis in beta-thalassaemic mice expressing lentivirus-encoded human beta-globin. Nature 2000; 406(6791):82-86.

    Google Scholar 

  31. Marsh M, Helenius A. Virus entry into animal cells. Adv Virus Res 1989; 36:107-151.

    Google Scholar 

  32. Burns JC, Friedmann T, Driever W et al. Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: concentration to very high titer and efficient gene transfer into mammalian and nonmammalian cells. Proc Natl Acad Sci USA 1993; 90(17):8033-8037.

    Google Scholar 

  33. Gasmi M, Glynn J, Jin MJ et al. Requirements for efficient production and transduction of human immunodeficiency virus type 1-based vectors. J Virol 1999; 73(3):1828-1834.

    Google Scholar 

  34. Kim VN, Mitrophanous K, Kingsman SM et al. Minimal requirement for a lentivirus vector based on human immunodeficiency virus type 1. J Virol 1998; 72(1):811-816.

    Google Scholar 

  35. Trono D. HIV accessory proteins: Leading roles for the supporting cast. Cell 1995; 82(2):189-192.

    Google Scholar 

  36. Deacon NJ, Tsykin A, Solomon A et al. Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients. Science 1995; 270(5238):988-991.

    Google Scholar 

  37. Baba TW, Liska V, Khimani AH et al. Live attenuated, multiply deleted simian immunodeficiency virus causes AIDS in infant and adult macaques. Nat Med 1999; 5(2):194-203.

    Google Scholar 

  38. Wyand MS, Manson KH, Garcia-Moll M et al. Vaccine protection by a triple deletion mutant of simian immunodeficiency virus. J Virol 1996; 70(6):3724-3733.

    Google Scholar 

  39. Desrosiers RC, Lifson JD, Gibbs JS et al. Identification of highly attenuated mutants of simian immunodeficiency virus. J Virol 1998; 72(2):1431-1437.

    Google Scholar 

  40. Chinnasamy D, Chinnasamy N, Enriquez MJ et al. Lentiviral-mediated gene transfer into human lymphocytes: role of HIV-1 accessory proteins. Blood 2000; 96(4):1309-1316.

    Google Scholar 

  41. Dull T, Zufferey R, Kelly M et al. A third-generation lentivirus vector with a conditional packaging system. J Virol 1998; 72(11):8463-8471.

    Google Scholar 

  42. Miyoshi H, Blomer U, Takahashi M et al. Development of a self-inactivating lentivirus vector. J Virol 1998; 72(10):8150-8157.

    Google Scholar 

  43. Zufferey R, Dull T, Mandel RJ et al. Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. J Virol 1998; 72(12):9873-80.

    Google Scholar 

  44. Yee JK, Moores JC, Jolly DJ et al. Gene expression from transcriptionally disabled retroviral vectors. Proc Natl Acad Sci USA 1987; 84(15):5197-201.

    Google Scholar 

  45. Yu SF, von Ruden T, Kantoff PW et al. Self-inactivating retroviral vectors designed for transfer of whole genes into mammalian cells. Proc Natl Acad Sci USA 1986; 83(10):3194-3198.

    Google Scholar 

  46. Kotsopoulou E, Kim VN, Kingsman AJ et al. A Rev-independent human immunodeficiency virus type 1 (HIV-1)-based vector that exploits a codon-optimized HIV-1 gag-pol gene. J Virol 2000;74(10):4839-4852.

    Google Scholar 

  47. Maldarelli F, Martin MA, Strebel K. Identification of posttranscriptionally active inhibitory sequences in human immunodeficiency virus type 1 RNA: Novel level of gene regulation. J Virol1991; 65(11):5732-5743.

    Google Scholar 

  48. Nasioulas G, Zolotukhin AS, Tabernero C et al. Elements distinct from human immunodeficiency virus type 1 splice sites are responsible for the Rev dependence of env mRNA. J Virol 1994;68(5):2986-2993.

    Google Scholar 

  49. Olsen HS, Cochrane AW, Rosen C. Interaction of cellular factors with intragenic cis-acting repressive sequences within the HIV genome. Virology 1992; 191(2):709-715.

    Google Scholar 

  50. Schwartz S, Campbell M, Nasioulas G et al. Mutational inactivation of an inhibitory sequence in human immunodeficiency virus type 1 results in Rev-independent gag expression. J Virol 1992;66(12):7176-7182.

    Google Scholar 

  51. Schwartz S, Felber BK, Pavlakis GN. Distinct RNA sequences in the gag region of human immunodeficiency virus type 1 decrease RNA stability and inhibit expression in the absence of Rev protein. J Virol 1992; 66(1):150-159.

    Google Scholar 

  52. Haas J, Park EC, Seed B. Codon usage limitation in the expression of HIV-1 envelope glycoprotein. Curr Biol 1996; 6(3):315-324.

    Google Scholar 

  53. Cui Y, Iwakuma T, Chang LJ. Contributions of viral splice sites and cis-regulatory elements to lentivirus vector function. J Virol 1999; 73(7):6171-6176.

    Google Scholar 

  54. Baur AS, Sawai ET, Dazin P et al. HIV-1 Nef leads to inhibition or activation of T cells depending on its intracellular localization. Immunity 1994; 1(5):373-384.

    Google Scholar 

  55. Mahalingam S, MacDonald B, Ugen KE et al. In vitro and in vivo tumor growth suppression by HIV-1 Vpr. DNA Cell Biol 1997; 16(2):137-143.

    Google Scholar 

  56. Murphy KM, Sweet MJ, Ross IL et al. Effects of the tat and nef gene products of human immunodeficiency virus type 1 (HIV-1) on transcription controlled by the HIV-1 long terminal repeat and on cell growth in macrophages. J Virol 1993; 67(12):6956-6964.

    Google Scholar 

  57. Ryan-Graham MA, Peden KW. Both virus and host components are important for the manifestation of a Nef-phenotype in HIV-1 and HIV-2. Virology 1995; 213(1):158-168.

    Google Scholar 

  58. Stewart SA, Poon B, Jowett JB et al. Lentiviral delivery of HIV-1 Vpr protein induces apoptosis in transformed cells. Proc Natl Acad Sci USA 1999; 96(21):12039-12043.

    Google Scholar 

  59. Yao XJ, Mouland AJ, Subbramanian RA et al. Vpr stimulates viral expression and induces cell killing in human immunodeficiency virus type 1-infected dividing Jurkat T cells. J Virol 1998;72(6):4686-4693.

    Google Scholar 

  60. Chen ST, Iida A, Guo L et al. Generation of packaging cell lines for pseudotyped retroviral vectors of the G protein of vesicular stomatitis virus by using a modified tetracycline inducible system. Proc Natl Acad Sci USA 1996; 93(19):10057-10062.

    Google Scholar 

  61. Ory DS, Neugeboren BA, Mulligan RC. A stable human-derived packaging cell line for production of high titer retrovirus/vesicular stomatitis virus G pseudotypes. Proc Natl Acad Sci U A1996; 93(21):11400-11406.

    Google Scholar 

  62. Kafri T, van Praag H, Ouyang L et al. A packaging cell line for lentivirus vectors. J Virol 1999;73(1):576-584.

    Google Scholar 

  63. Klages N, Zufferey R, Trono D. A stable system for the high-titer production of multiply attenuated lentiviral vectors. Mol Ther 2000; 2(2):170-176.

    Google Scholar 

  64. Xu K, Ma H, McCown TJ et al. Generation of a stable cell line producing high-titer self-inactivating lentiviral vectors. Mol Ther 2001; 3(1):97-104.

    Google Scholar 

  65. Hottinger AF, Azzouz M, Deglon N et al. Complete and long-term rescue of lesioned adult motoneurons by lentiviral-mediated expression of glial cell line-derived neurotrophic factor in the facial nucleus. J Neurosci 2000; 20(15):5587-5593.

    Google Scholar 

  66. Henderson CE, Phillips HS, Pollock RA et al. GDNF: A potent survival factor for motoneurons present in peripheral nerve and muscle. Science 1994; 266(5187):1062-1064.

    Google Scholar 

  67. Ferri CC, Moore FA, Bisby MA. Effects of facial nerve injury on mouse motoneurons lacking the p75 low-affinity neurotrophin receptor. J Neurobiol 1998; 34(1):1-9.

    Google Scholar 

  68. Kou SY, Chiu AY, Patterson PH. Differential regulation of motor neuron survival and choline acetyltransferase expression following axotomy. J Neurobiol 1995; 27(4):561-572.

    Google Scholar 

  69. Kordower JH, Emborg ME, Bloch J et al. Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease. Science 2000; 290(5492):767-773.

    Google Scholar 

  70. Emborg ME, Ma SY, Mufson EJ et al. Age-related declines in nigral neuronal function correlate with motor impairments in rhesus monkeys. J Comp Neurol 1998; 401(2):253-265.

    Google Scholar 

  71. Neufeld EF. Lysosomal storage diseases. Annu Rev Biochem 1991; 60:257-280.

    Google Scholar 

  72. Danciger M, Blaney J, Gao YQ et al. Mutations in the PDE6B gene in autosomal recessive retinitis pigmentosa. Genomics 1995; 30(1):1-7.

    Google Scholar 

  73. McLaughlin ME, Ehrhart TL, Berson EL et al. Mutation spectrum of the gene encoding the beta subunit of rod phosphodiesterase among patients with autosomal recessive retinitis pigmentosa. Proc Natl Acad Sci USA 1995; 92(8):3249-3253.

    Google Scholar 

  74. Pittler SJ, Baehr W. Identification of a nonsense mutation in the rod photoreceptor cGMP phosphodiesterase beta-subunit gene of the rd mouse. Proc Natl Acad Sci USA 1991; 88(19):8322-8326.

    Google Scholar 

  75. Suber ML, Pittler SJ, Qin N et al. Irish setter dogs affected with rod/cone dysplasia contain a nonsense mutation in the rod cGMP phosphodiesterase beta-subunit gene. Proc Natl Acad Sci USA 1993; 90(9):3968-3972.

    Google Scholar 

  76. Takahashi M, Miyoshi H, Verma IM et al. Rescue from photoreceptor degeneration in the rd mouse by human immunodeficiency virus vector-mediated gene transfer. J Virol 1999; 73(9):7812-7816.

    Google Scholar 

  77. Havenga M, Hoogerbrugge P, Valerio D et al. Retroviral stem cell gene therapy. Stem Cells 1997;15(3):162-179.

    Google Scholar 

  78. Kiem HP, Andrews RG, Morris J et al. Improved gene transfer into baboon marrow repopulating cells using recombinant human fibronectin fragment CH-296 in combination with interleukin-6, stem cell factor, FLT-3 ligand, and megakaryocyte growth and development factor. Blood 1998;92(6):1878-1886.

    Google Scholar 

  79. Guenechea G, Gan OI, Inamitsu T et al. Transduction of human CD34+ CD38-bone marrow and cord blood-derived SCID-repopulating cells with third-generation lentiviral vectors. Mol Ther2000; 1(6):566-573.

    Google Scholar 

  80. Haas DL, Case SS, Crooks GM et al. Critical factors influencing stable transduction of human CD34(+) cells with HIV-1-derived lentiviral vectors. Mol Ther 2000; 2(1):71-80.

    Google Scholar 

  81. Ramezani A, Hawley TS, Hawley RG. Lentiviral vectors for enhanced gene expression in human hematopoietic cells. Mol Ther 2000; 2(5):458-469.

    Google Scholar 

  82. Salmon P, Kindler V, Ducrey O et al. High-level transgene expression in human hematopoietic progenitors and differentiated blood lineages after transduction with improved lentiviral vectors. Blood 2000; 96(10):3392-3398.

    Google Scholar 

  83. Sirven A, Pflumio F, Zennou V et al. The human immunodeficiency virus type-1 central DNA flap is a crucial determinant for lentiviral vector nuclear import and gene transduction of human hematopoietic stem cells. Blood 2000; 96(13):4103-4110.

    Google Scholar 

  84. Woods NB, Fahlman C, Mikkola H et al. Lentiviral gene transfer into primary and secondary NOD/SCID repopulating cells. Blood 2000; 96(12):3725-3733.

    Google Scholar 

  85. Chang HK, Gendelman R, Lisziewicz J et al. Block of HIV-1 infection by a combination of antisense tat RNA and TAR decoys: A strategy for control of HIV-1. Gene Ther 1994; 1:208-216.

    Google Scholar 

  86. Kim JH, McLinden RJ, Mosca JD et al. Inhibition of HIV-1 replication by sense and antisense rev response elements in HIV-based retroviral vectors. J Acquir Immune Defic Syndr Hum Retrovirol1996; 12:343-351.

    Google Scholar 

  87. Ho DD, Pomerantz RJ, Kaplan JC. Pathogenesis of infection with human immunodeficiency virus. N Engl J Med 1987; 317:278-286.

    Google Scholar 

  88. Buck HM, Koole LH, van Genderen MHP et al. Phosphate-methylated DNA aimed at HIV-1 RNA loops and integrated DNA inhibits viral infectivity. Science 1990; 248:208-212.

    Google Scholar 

  89. Lisziewicz J, Sun D, Klotman M et al. Specific inhibition of human immunodeficiency virus type1 replication by antisense oligonucleotides. Proc Natl Acad Sci USA 1988; 89:11209-11213.

    Google Scholar 

  90. Sullenger BA, Gallardo HF, Ungers GE et al. Overexpression of TAR sequences renders cells resistant to human immunodeficiency virus replication. Cell 1990; 63:601-608.

    Google Scholar 

  91. Lisziewicz J, Peng B, Ensoli B et al. An autoregulated dual-function antitat gene for human immunodeficiency virus type 1 gene therapy. J Virol 1995; 69:206-212.

    Google Scholar 

  92. Rosenzweig M, Johnson RP, Lisziewicz J et al. Transduction of CD34+ hematopoietic progenitor cells with an anti-tat gene protects T-cell and macrophage progeny from AIDS virus infection. J Virol 1997; 71:2740-2746.

    Google Scholar 

  93. Morgan RA, Walker R. Gene therapy for AIDS using retroviral mediated gene transfer to deliver HIV-1 antisense TAR and transdominant Rev protein genes to syngeneic lymphocytes in HIV-1 infected identical twins. Hum Gene Ther 1996; 7:1281-1306.

    Google Scholar 

  94. Sarver N, Cantin EM, Chang PS et al. Ribozymes as potential anti-HIV-1 therapeutic agents. Science 1990; 247:1222-1225.

    Google Scholar 

  95. Ojwang JO, Hampel A, Looney DJ et al. Inhibition of human immunodeficiency virus type 1 expression by a hairpin ribozyme. Proc Natl Acad Sci USA 1992; 89:10802-10806.

    Google Scholar 

  96. Bai J, Gorantla S, Banda N et al. Characterization of anti-CCR5 ribozyme-transduced CD34+ hematopoietic progenitor cells in vivo. Molec Ther 2000; 1:244-254.

    Google Scholar 

  97. Bauer G, Kohn DB, Zaia JA et al. Inhibition of human immunodeficiency virus-1 (HIV-1) replication after transduction of granulocyte colony-stimulating factor-mobilized CD34+ cells from HIV-1 infected donors using retroviral vectors containing anti-HIV-1 genes. Blood 1997; 89:2259.

    Google Scholar 

  98. Woffendin C, Ranga U, Yang Z et al. Expression of a protective gene prolongs survival of T-lymphocytes in human immunodeficiency virus-infected patients. Proc Natl Acad Sci USA 1996;93:2889-2894.

    Google Scholar 

  99. Ranga U, Woffendin C, Verma S et al. Enhanced T cell engraftment after retroviral delivery of an antiviral gene in HIV-infected individuals. Proc Natl Acad Sci (USA) 1998; 95:1201-1206.

    Google Scholar 

  100. Caputo A, Rossi C, Bozzini R et al. Studies on the effect of the combined expression of anti-tat and anti-rev genes on HIV-1 replication. Gene Ther 1997; 4:288-295.

    Google Scholar 

  101. Chinen J, Aguilar-Cordova E, Ng-Tang D et al. Protection of primary human T-cells from HIV-1 infection by Trev: A transdominant fusion gene. Hum Gene Ther 1997; 8:861-868.

    Google Scholar 

  102. Smith SM, Markham RB, Jeang KT. Conditional reduction of human immunodeficiency virus type 1 replication by a gain-of-herpes simplex virus 1 thymidine kinase function. Proc Natl Acad Sci USA 1996; 93:7955-7960.

    Google Scholar 

  103. Curiel TJ, Cook DR, Wang Y et al. Long-term inhibition of clinical and laboratory human immunodeficiency virus strains in human T-cell lines containing an HIV-regulated diphtheria toxin A chain gene. Hum Gene Ther 1993; 4:741-747.

    Google Scholar 

  104. Schnell MJ, Johnson JE, Buonocore L et al. Construction of a novel virus that targets HIV-1-infected cells and controls HIV-1 infection. Cell 1997; 90:849-857.

    Google Scholar 

  105. Mebatsion T, Finke S, Weiland F et al. A CXCR4/CD4 pseudotype rhabdovirus that selectively infects HIV-1 envelope protein-expressing cells. Cell 1997; 90:841-847.

    Google Scholar 

  106. Yang AG, Chen S, Yao C et al. Phenotypic knockout of HIV-1 type 1 chemokine coreceptor CCR-5 by intrakines as potential therapeutic approach for HIV-1 infection. Proc Natl Acad Sci USA 1997; 94:11567-11572.

    Google Scholar 

  107. Chen JD, Bai X, Yang AG et al. Inactiviation of HIV-1 chemokine co-receptor CXCR-4 by a novel intrakine strategy. Nat Med 1997; 3:1110-1116.

    Google Scholar 

  108. Yang AG, Zhang X, Torti FJ et al. Anti-HIV type 1 activity of wild-type and functional defective RANTES intrakine in primary human lymphocytes. Hum Gene Ther 1998; 9:2005-2018.

    Google Scholar 

  109. Buonocore L, Rose JK. Blockade of human immunodeficiency virus type 1 production in CD4+ T cells by an intracellular CD4 expressed under control of the viral long terminal repeat. Proc Natl Acad Sci USA 1993; 90:2695-2699.

    Google Scholar 

  110. Marasco WA, Haseltine WA, Chen S-Y. Design, intracellular expression, and activity of a human anti-human immunodeficiency virus type 1 gp120 single-chain antibody. Proc Natl Acad Sci USA1993; 90:7889-7893.

    Google Scholar 

  111. Duan L, Bagasra O, Laughlin MA et al. Potent inhibition of human immunodeficiency virus type1 replication by an intracellular anti-Rev single-chain antibody. Proc Natl Acad Sci (USA) 1994;91:5075-5079.

    Google Scholar 

  112. Levin R, Mhashilkar AM, Dorfman T et al. Inhibition of early and late events of the HIV-1 replication cycle by cytoplasmic Fab intrabodies against the matrix protein, p17. Mol Med 1997;3:96-110.

    Google Scholar 

  113. Rondon IJ, Marasco WA. Intracellular antibodies (intrabodies) for gene therapy of infectious diseases. Ann Rev Microbiol 1997; 51:257-283.

    Google Scholar 

  114. Levy-Mintz P, Duan L, Zhang H et al. Intracellular expression of single-chain variable fragments to inhibit early stages of the viral life cycle by targeting human immunodeficiency virus type 1 integrase. J Virol 1996; 70:8821-8832.

    Google Scholar 

  115. Mitsuya H, Yarchoan R, Broder S. Molecular targets for AIDS therapy. Science 1990;249:1533-1543.

    Google Scholar 

  116. Embretson J, Zupancic M, Ribas JS et al. Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature 1993; 362:357-362.

    Google Scholar 

  117. Michael N, Morrow P, Mosca J et al. Induction of HIV-1 expression is associated with a shift in RNA splicing patterns. J Virol 1991; 65:1291-1303.

    Google Scholar 

  118. Palella JrF, Delaney KM, Moorman AC eal. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998; 338:853-860.

    Google Scholar 

  119. Gulick Rm, Mellors JW, Havlir D et al. Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. N Engl J Med 1997; 337:734-739.

    Google Scholar 

  120. Cavert W, Notermans DW, Staskus K et al. Kinetics of response in lymphoid tissues to antiretroviral therapy of HIV-1 infection. Science 1997; 276:960-964.

    Google Scholar 

  121. Wong JK, Gunthard HF, Havlir DV et al. Reduction of HIV-1 in blood and lymph nodes following potent antiretroviral therapy and the virologic correlates of treatment failure. Proc Natl Acad Sci USA 1997; 94:12574-12579.

    Google Scholar 

  122. Ho DD. Toward HIV eradication or remission: The tasks ahead. Science 1998; 280:1866-1867.

    Google Scholar 

  123. D'Arminio Monforte A, Testa L, Adorni E et al. Clinical outcome and predictive factors of failure of highly active antiretroviral therapy in antiretroviral-experienced patients in advanced stages of HIV-1 infection. AIDS 1998; 12:1631-1637.

    Google Scholar 

  124. Ledergerber B, Egger M, Opravil M et al. Clinical progression and virological failure on highly active antiretroviral therapy in HIV-1 patients: A prospective cohort study. Swiss Cohort Study. Lancet 1999; 353:863-868.

    Google Scholar 

  125. Aukrust P, Muller F, Lien E et al. Tumor necrosis factor (TNF) system levels in human immunodeficiency virus-infected patients during highly active antiretroviral therapy: Persistent TNF activation is associated with virologic and immunologic treatment failurehuman immunodeficiency virusinfected patients during highly. J Infect Dis 1999; 179:74-82.

    Google Scholar 

  126. Lucas GM, Chaisson RE, Moore RD. Highly active antiretroviral therapy in a large urban clinic: Risk factors for viroogic failure and adverse drug reactions. Ann Intern Med 1999; 131:81-87.

    Google Scholar 

  127. Wit FW, van Leeuwen R, Weverling GJ et al. Outcome and predictors of failure of highly active retroviral therapy: One year follow-up of a cohort of human immunodeficiency virus type 1-infected persons. J Infect Dis 1999; 179:790-798.

    Google Scholar 

  128. Evans TG, Bonnez W, Soucier HR et al. Highly active antiretroviral therapy results in a decrease in CD8+ T cell activation and preferential reconstitution of the peripheral CD4+ T cell population with memory rather than naive cells. Antiviral Res 1998; 39:163-173.

    Google Scholar 

  129. Bucy RP, Hockett RD, Derdeyn CA et al. Initial increase in blood CD4+ lymphocytes after HIV antiretroviral therapy reflects redistribution from lymphoid tissues. J Clin Invest 1999;103:1391-1398.

    Google Scholar 

  130. Haase AT. Population biology of HIV-1 infection: viral and CD4+ T cell demographics and dynamics in lymphatic tissue. Ann Rev Immunol 1999; 17:625-656.

    Google Scholar 

  131. Zanussi S, Simonelli C, Bartolin MT et al. Immunological changes in peripheral blood and in lymphoid tissue after treatment of HIV-infected subjects with highly active anti-retroviral therapy (HAART) or HAART + IL-2. Cliin Exp Immunol 1999; 116:486-492.

    Google Scholar 

  132. Martinon F, Michelet C, Peguillet I et al. Persistent alterations in T-cell repertoire, cytokine and chemokine receptor gene expression after 1 year of highly active antiretroviral therapy. AIDS 1999;13:185-194.

    Google Scholar 

  133. Finzi D, Hermankova M, Pierson T et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 1997; 278:1295-1300.

    Google Scholar 

  134. Natarajan V, Bosche M, Metcalf JA et al. HIV-1 replication in patients with undetectable plasma virus receiving HAART, HIghly active antiretroviral therapy. Lancet 1999; 353:119-120.

    Google Scholar 

  135. Chun TW, Engel D, Berrey MM et al. Early establishment of a pool of latently infected, resting CD4(+) T cells during primaryHIV-1 infection. Proc Natl Acad Sci USA 1998; 95:8869-8873.

    Google Scholar 

  136. Finzi D, Blankson J, Siliciano JD et al. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nature Med 1999;5:512-517.

    Google Scholar 

  137. Zhang H, Dornadula G, Beaumont M et al. Human immunodeficiency virus type 1 in the semen of men receiving highly active antiretorviral therapy. N Engl J Med 1998; 339:1803-1809.

    Google Scholar 

  138. Schapiro JM, Winters MA, Lawrence J et al. Clinical cross-resistance between the HIV-1 protease inhibitors saquinavir and indinavir and correlations with genotypic mutations. AIDS 1999;13:359-365.

    Google Scholar 

  139. Loveday C, Devereux H, Huckett L et al. High prevalence of multiple drug resistance mutations in a UK HIV/AIDS patient population. AIDS 1999; 13:627-628.

    Google Scholar 

  140. Vandamme AM, Van Laethem K, DeClerq E. Managing resistance to anti-HIV drugs: An important consideration for effective disease management. Drugs 199; 57:337-361.

  141. Jimenez-Nacher I, Rodriguez-Rosado R, Anton P et al. Virological failure and adherence to antiretroviral therapy in HIV-infected patients. Int Conf AIDS 1998; 12:591, 32350a

    Google Scholar 

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  1. Department of Virology, Beckman Research Institute City of Hope, Duarte, California, 91010

    Jiing-Kuan Yee & John A. Zaia

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  1. Jiing-Kuan Yee
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Yee, JK., Zaia, J.A. Prospects for Gene Therapy Using HIV-Based Vectors. Somat Cell Mol Genet 26, 159–174 (2001). https://doi.org/10.1023/A:1021034931852

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