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Animal Models of Gene Therapy for AIDS

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Gene Therapy for HIV Infection

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Abstract

An appropriate test system for AIDS gene therapies must possess several features. It must readily allow the introduction of gene therapeutics to be tested and must reproduce, at least in part, the pathogenesis of HIV-1 in infected people. The value of animal models for testing anti-HIV-1 gene therapy is clear from the inadequacy of tissue culture systems in reproducing the pathogenesis of patient derived strains of HIV-1. T lymphoblastoid cell lines (T-LCL) are not permissive for most clinical isolates of HIV-1 since they lack CCR5,1 and primary T cells are difficult to maintain for long periods without compromising their diversity. Furthermore, in tissue culture four of the nine genes of HIV-1 are dispensable for replication,2 while in pathogenic infections in humans, all nine genes are universally maintained.3 These deficiencies have led to the use of several animal models for the study of HIV-1 pathogenesis. Several model systems use immunodeficient mice engrafted with human immune cells while other models use one of several species of macaque infected with SIV, a virus which is highly related to HIV-2 and more distantly related to HIV-1.4 Some of these animal models of HIV and SIV pathogenesis have been modified to allow the testing of potential gene therapeutic agents for human and simian AIDS.

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References

  1. Berger EA. HIV entry and tropism: the chemokine receptor connection. AIDS 1997; 11: S3 – S16.

    Google Scholar 

  2. Luciw P. Human immunodeficiency viruses and their replication. In: Fields BN, Knipe DM, Howley PM et al, eds. Fields Virology. 3`d ed. Philadelphia: Lippincott-Raven, 1996: 1881–1952.

    Google Scholar 

  3. Myers G, Korber B, Hahn BH et al. Human retroviruses and AIDS 1995. Los Alamos. Los Alamos National Laboratory, 1995.

    Google Scholar 

  4. Gardner MB, Luciw PA. Simian immunodeficiency viruses and their relationship to the human immunodeficiency viruses. AIDS 1988; 2 (suppl 1):S3-Slo.

    Google Scholar 

  5. Bosma GC, Custer RP, Bosma MJ. A severe combined immunodeficiency mutation in the mouse. Nature 1983; 301:527-530.

    Google Scholar 

  6. Mosier DE, Gulizia RJ, Baird SM et al. Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature 1988; 335: 256–259.

    Article  PubMed  CAS  Google Scholar 

  7. McCune JM, Namikawa R, Kaneshima H et al. The SCID-hu mouse murine model for the analysis of human hematolymphoid differentiation and function. Science 1988; 241: 1632–1639.

    Article  PubMed  CAS  Google Scholar 

  8. Torbett BE, Picchio G, Mosier DE. hu-PBL-SCID mice: a model for human immune function, AIDS, and lymphomagenesis. Immunol Rev 1991; 124: 139–164.

    Article  PubMed  CAS  Google Scholar 

  9. Carlsson R, Martensson C, Kalliomaki S et al. Human peripheral blood lymphocytes transplanted into SCID mice constitute an in vivo culture system exhibiting several parameters found in a normal humoral immune response and are a source of immunocytes for the production of human monoclonal antibodies. J Immunol 1992; 148: 1065–107.

    PubMed  CAS  Google Scholar 

  10. Mosier D, Gulizia R, Baird SM et al. Human immunodeficiency vi- rus infection of human-PBL-SCID mice. Science 1991; 251791-794.

    Google Scholar 

  11. Boyle MJ, Connors M, Flanigan ME et al. The human HIV/peripheral blood lymphocyte (PBL)-SCID mouse. J Immunol 1995; 154: 6612–6623.

    PubMed  CAS  Google Scholar 

  12. Mosier D, Gulizia RJ, MacIsaac P et al. Rapid loss of CD4+ T cells in human-PBL-SCID mice by noncytopathic HIV isolates. Science 1993; 260: 689–692.

    Article  Google Scholar 

  13. Connor R, Mohri H, Cao Y et al. Increased viral burden and cytopathogenicity correlate temporally with CD4+ T lymphocyte decline and clinical progression in HIV-1 infected individuals. J Virol 1993; 67:1772–1777.

    Google Scholar 

  14. Mosier DE, Gulizia RJ, Maclssac PD et al. Resistance to human immunodeficiency virus 1 infection of SCID mice reconstituted with peripheral blood lymphocytes from donors vaccinated with vaccinia gp 160 and recombinant gp 160. Proc Natl Acad Sci USA 1993; 86: 2365–2369.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  16. McCune JM. Development and applications of the SCID-hu mouse model. Seminars in Immunology 1996; 8: 187–196.

    Article  PubMed  CAS  Google Scholar 

  17. Namikawa R, Weilbaecher KN, Kaneshima H et al. Long-term human hematopoiesis in the SCID-hu mouse. J Exp Med 1990; 172: 1055–1063.

    Article  PubMed  CAS  Google Scholar 

  18. Stanley SK, McCune JM, Kaneshima H et al. HIV infection of the human thymus and disruption of the thymic microenvironment in the SCID-hu mouse. J Exp Med 1993; 178: 1151–1163.

    Google Scholar 

  19. Aldrovandi GM, Feuer G, Gao L et al. The SCID-hu mouse as a model for HIV-1 infection. Nature 1993; 363 (6431)732-736.

    Google Scholar 

  20. Bonyhadi ML, Rabin L, Salimi S et al. HIV induces thymus depletion in vivo. Nature 1993; 363:728-736.

    Google Scholar 

  21. Jamieson BD, Aldrovandi GM, Planelles V et al. Requirement of HIV-1 nef for in vivo replication and pathogenicity. J Virol 1994; 68:3478-3485.

    Google Scholar 

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

    Google Scholar 

  23. Kaneshima H, Su L, Bonyhadi ML et al. Rapid-high, syncytium-inducing isolates of HIV-1 cytopathicity in the human thymus of the SCID-hu mouse. J Virol 1994; 68: 8188–8192.

    Google Scholar 

  24. Akkina RK, Rosenblatt JD, Campbell AG et al. Modeling human lymphoid precursor cell gene therapy in the SCID-hu mouse. Blood 1994; 84: 1393–1398.

    Google Scholar 

  25. Sutherland HJ, Lansdorp PM, Henkelman DH et al. Functional characterization of individual human hematopoietic stem cells cultured at limiting dilution on supportive marrow stromal layers. Proc Natl Acad Sci USA 1990; 87: 3584–3588.

    Google Scholar 

  26. Champseix C, Maréchal V, Khazaal I et al. A cell surface marker gene transferred with a retroviral vector into CD34+ cord blood cells is expressed by their T cell progeny in the SCID-hu thymus. Blood 1996; 88(1):1o7-n3.

    Google Scholar 

  27. An DS, Koyanagi Y, Zhao J-Q et al. High-efficiency transduction of human lymphoid progenitor cells and expression in differentiated T cells. J Virol 1997; 71(2):1397–1404.

    Google Scholar 

  28. Bonyhadi ML, Moss K, Voytovich A et al. RevMio-expressing T cells derived in vivo from transduced human hematopoietic stem-progenitor cells inhibit human immunodeficiency virus replication. J Virol 1997; 71(6):47o7-4716.

    Google Scholar 

  29. Bevec D, Dobrovnik M, Hauber J et al. Inhibition of human immunodefiency 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 1992; 899870-9874.

    Google Scholar 

  30. Malim MH, Freimuth WW, Liu J et al. Stable expression of transdominant Rev protein in human T cells inhibits human immunodefiency virus replication. J Exp Med 1992; 176: 1197–1201.

    CAS  Google Scholar 

  31. Kyoizumi S, Baum C, Kaneshima H et al. Implantation and maintenance of functional human bone marrow into SCID-hu mice. Blood 1992; 79: 1704–1711.

    Google Scholar 

  32. Chen BP, Galy A, Kyoizumi S et al. Engraftment of human hematopoietic precursor cells with secondary transfer potential in SCID-hu mice. Blood 1994; 84(8):2497–25o5.

    Google Scholar 

  33. Su L, Lee R, Bonyhadi M et al. Hematopoietic stem cell-based gene therapy for acquired immunodeficiency syndrome: efficient transduction and expression of RevMio in myeloid cells in vivo and in vitro. Blood 1997; 89(7):2283-229o.

    Google Scholar 

  34. Kamel-Reid S, Dick JE. Engraftment of immune deficient mice with human hematopoietic stem cells. Science 1988; 242: 1706–1709.

    Article  PubMed  CAS  Google Scholar 

  35. Lapidot T, Pflumio F, Doedens F et al. Cytokine stimulation of multilineage human hematopoiesis from immature cells transplanted into SCID mice. Science 1992; 255: 1137–1141.

    Article  PubMed  CAS  Google Scholar 

  36. Kollmann TR, Kim A, Zhuang X et al. Multilineage hematopoiesis and peripheral reconstitution of SCID mice with human lymphoid and myeloid cells following transplantation with human fetal bone marrow. Proc Nall Acad Sci USA 1994; 91: 8032–8036.

    Google Scholar 

  37. Yurasov S, Kollmann TR, Kim A et al. SCID mice engrafted with human T cells, B cells, and myeloid cells after transplantation with human fetal bone marrow or liver cells and implanted with human fetal thymus: a model for studying human gene therapy. Blood 1997; 89 (5):1800–1810.

    Google Scholar 

  38. Laurent-Crawford AG, Drust B, Muller S et al. The cytopathic effect of HIV is associated with apoptosis. Virology 1991; 185: 829–839.

    Article  PubMed  CAS  Google Scholar 

  39. Terai C, Kornbluth RS, Pauza CD et al. Apoptosis as a mechanism of cell death in cultured lymphoblasts acutely infected with HIV-1. J Clin Invest 1991; 87: 1710–1715.

    Article  PubMed  CAS  Google Scholar 

  40. Walker BD, Chakrabarti S, Moss B et al. HIV-specific cytotoxic T lymphocytes in seropositive individuals. Nature 1987; 32$345-348.

    Google Scholar 

  41. Tanneau R, McChesney M, Lopez O et al. Primary cytotoxicity against the envelope glycoprotein of human immunodeficiency virus-1: evidence for antibody-dependent cellular cytotoxicity in vivo. J Infec Dis 1990; 162:837-843.

    Google Scholar 

  42. Gary RF. Potential mechanisms for the cytopathic properties of HIV. AIDS 1989; 3683-694.

    Google Scholar 

  43. Lifson JD, Feinberg MB, Reyes GR et al. Induction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein. Nature 1986; 323: 725–728.

    Article  PubMed  CAS  Google Scholar 

  44. Su L, Kaneshima H, Bonyhadi M. HIV-1 induced thymocyte depletion is associated with indirect cytopathicity and infection of progenitor cells in vivo. Immunity 1995; 225-36.

    Google Scholar 

  45. Jamieson BD, Uittenbogaart CH, Schmid I et al. High viral burden and rapid CD4+ cell depletion in human immunodeficiency virus type 1-infected SCID-hu mice suggest direct viral killing of thymocytes in vivo. J Virol 1997; 71 (n): 8245–8253.

    PubMed  CAS  Google Scholar 

  46. Fultz P, McClure H, Swenson R et al. Persistent infection of chimpanzees with human T-lymphotropic virus type III/lymphadenopathy-associated virus: a potential model for acquired immunodeficiency syndrome. J Virol 1986; 58; 116–124.

    PubMed  CAS  Google Scholar 

  47. Fultz P, McClure H, Swenson R et al. HIV infection of chimpanzees as a model for testing chemotherapeutics. Intervirology 1989; 3oS1:51–58.

    Google Scholar 

  48. Agy MB, Frumkin LR, Corey L et al. Infection of Macaca nemestrina by human immunodeficiency virus type-1. Science 1992; 257: 103–106.

    Article  PubMed  CAS  Google Scholar 

  49. Letvin NL, Daniel MD, Sehgal PK et al. Induction of AIDS-like disease in macaque monkeys with T cell tropic retrovirus STLV-III. Science 1985; 230: 71–73.

    Google Scholar 

  50. van Beusechem VW, Valerio D. Gene transfer into hematopoietic stem cells of nonhuman primates. Human Gene Therapy 1996; 7: 1649–1668.

    Article  PubMed  Google Scholar 

  51. van Bekkum DW. The rhesus monkey as a preclinical model for bone marrow transplantation. Transplant Proc 1978; 10: 105–111.

    PubMed  Google Scholar 

  52. Anderson WF, Kantoff P, Eglitis M et al. Gene transfer and expression in nonhuman primates using retroviral vectors. In: Cold Spring Harbor Symp Quant Biol 1986; 51: 1073–1081.

    Google Scholar 

  53. Kantoff PW, Gillio AP, McLachlin JR et al. Expression of human adenosine deaminase in nonhuman primates after retrovirus-mediated gene transfer. J Exp Med1987; 166:219-234.

    Google Scholar 

  54. Cornetta K, Wieder R, Anderson WF. Gene transfer into primates and prospects for gene therapy in humans. Prog Nucl Acid Res Mol Biol 1990; 36: 311–322.

    Google Scholar 

  55. Bodine DM, McDonagh KT, Brandt SJ et al. Development of a high-titer retrovirus producer cell line capable of gene transfer into rhesus monkey hematopoietic stem cells. Proc Natl Acad Sci USA 1990; 87:3738-3742.

    Google Scholar 

  56. van Beusechem VW, Kukler A, Einerhand M et al. Expression of human ADA in mice transpalnted with hemopoietic stem cells infected with amphotropic retroviruses. J Exp Med 1990; 172: 729–736.

    Google Scholar 

  57. Andrews RG, Bryant EM, Bartelmez SH et al. CD34+ marrow cells, devoid of T and B lymphocytes, reconstitute stable lymphopoiesis and myelopoiesis in lethally irradiated allogenic baboons. Blood 1992; 80: 1693–1701.

    Google Scholar 

  58. Xu LC, Karlsson S, Byrne ER et al. Long-term in vivo expression of the human glucocerebrosidase gene in nonhuman primates after CD34+ hematopoietic cell transduction with cell-free retroviral vector preparations. Proc Natl Acad Sci USA 1995; 92: 4372–4376.

    Google Scholar 

  59. Kaptein LCM, van Beusechem VW, Riviere I et al. Long-term in vivo expression of the MFG-ADA retroviral vector in rhesus monkeys transplanted with transduced bone marrow cells. Hum Gene Ther 1997; 8: 1605–1610.

    Article  PubMed  CAS  Google Scholar 

  60. van Beusechem VW, Kukler A, Heidt PJ et al. Long-term expression of human adenosine deaminase in rhesus monkeys transplanted with retrovirus-infected bone-marrow cells. Proc Nall Acad Sci USA 1992; 89: 764o - 7644.

    Google Scholar 

  61. Gerritsen WR, Wagemaker G, Jonker M et al. The repopulation capacity of bone marrow grafts following pretreatment with monoclonal antibodies against T lymphocytes in rhesus monkeys. Transplantation 1988; 45: 301–307.

    Article  PubMed  CAS  Google Scholar 

  62. Kingston R, Jenkinson EJ, Owen JJT. A single stem cell can recolonize an embryonic thymus producing phenotypically distinct T cell populations. Nature 1985; 317: 811–813.

    Article  PubMed  CAS  Google Scholar 

  63. van Ewijk W. T cell differentiation is influenced by thymic microenvironments. Annu Rev Immunol 1991; 9: 591–615.

    Google Scholar 

  64. Rosenzweig M, Marks DF, Zhu H et al. In vitro T lymphopoiesis of human and rhesus CD34+ progenitor cells. Blood 1996; 87: 4040–4048.

    PubMed  CAS  Google Scholar 

  65. Haynes BF, Denning S, Le PT et al. Human intrathymic T cell differentiation. Semin Immunol 1990; 2: 67–77.

    PubMed  CAS  Google Scholar 

  66. Terstappen WMM, Huang S, Picker LJ. Flow cytometric assessment of human T cell differentiation in thymus and bone marrow. Blood 1990; 70: 666–677.

    Google Scholar 

  67. Haynes BF, Martin ME, Kay HH. Early events in human T cell ontogeny. J Exp Med 1988; 168: 1061–1080.

    Article  PubMed  CAS  Google Scholar 

  68. Reimann KA, Waite BCD, Lee-Parritz DE et al. Use of human leukocyte-specific monoclonal antibodies for clinically immunophenotyping lymphocytes of rhesus monkeys. Cytometry 1994; 17: 102–108.

    Google Scholar 

  69. Rosenzweig M, Marks DF, Hempel D et al. In vitro lymphopoiesis: a model system for stem cell gene therapy in AIDS. J Med Primatol 1996; 25: 192–200.

    Article  PubMed  CAS  Google Scholar 

  70. Rosenzweig M, Marks DF, Hempel D et al. Transduction of CD34+ hematopoietic progenitor cells with an antitat gene protects T cell and macrophage progeny from AIDS infection. J Virol 1997; 71: 2740–2746.

    PubMed  CAS  Google Scholar 

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Authors
  1. Linda M. Kofeldt
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  2. David Camerini
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© 1998 Springer-Verlag Berlin Heidelberg

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Kofeldt, L.M., Camerini, D. (1998). Animal Models of Gene Therapy for AIDS. In: Gene Therapy for HIV Infection. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-11821-4_7

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  • DOI: https://doi.org/10.1007/978-3-662-11821-4_7

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-11823-8

  • Online ISBN: 978-3-662-11821-4

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