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Use of transgenic animals to study human retroviruses

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Abstract

The purpose of transgenic technology is to introduce a gene into the germline of an animal in order to investigate its proper expression in the appropriate cell types and its effect on cellular functions. This technology has been used to explore a wide variety of genetic and biological issues including stage- and tissue-specific gene expression, development, immunology, oncology, and gene therapy [1–3]. The intent of this article is to discuss the value of gene transfer technology for the study of mechanisms of viral pathogenesis. We will focus mainly on our experience with two experimental systems involving human T-lymphotropic virus Type 1 (HTLV-1) and human immunodeficiency virus Type 1 (HIV-1).

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References

  1. Gordon JW, Ruddle FH: Gene transfer into mouse embryos: production of transgenic mice by pronuclear injection. Meth Enzymol 101: 411–433, 1983

    Google Scholar 

  2. Brinster RL, Chen HY, Trumbauer ME, Yagle MK, Palmiter RD: Factors affecting the efficiencies of introducing foreign DNA into mice by microinjecting eggs. Proc Natl Acad Sci USA 82: 4438–4442, 1985

    Google Scholar 

  3. Scangos G, Bieberich C: Gene transfer into mouse. Adv Genet 24: 285–322, 1987

    Google Scholar 

  4. Gallo RC: The first human retrovirus. Sci Am 255: 88–98, 1986

    Google Scholar 

  5. Gallo RC: The AIDS virus. Sci Am 256: 46–56, 1987

    Google Scholar 

  6. Miyoshi I, Kubonishi I, Yoshimoto S, Agaki T, Ohtushi Y, Shiraiski Y, Nagata N, Hinuma Y: Type C virus particles in a cord T-cell line derived by co-cultivating normal human leukocytes and human leukemic T-cells. Nature 294: 770–771, 1981

    Google Scholar 

  7. Poiez BJ, Ruscetti FW, Reitz MS, Kalyanaraman VS, Gallo RC: Isolation of a new type C retrovirus (HTLV) in primary uncultured cells of a patient with Sezary T-cell leukemia. Nature 294: 268–271, 1981

    Google Scholar 

  8. Chen ISY, Quan SG, Golde DW: Human T-cell leukemia virus type II transforms normal lymphocytes. Proc Natl Acad Sci USA 80: 7006–7009, 1983

    Google Scholar 

  9. Popovic MP, Sarin PS, Robert-Guroff M, Kalyanaraman VS, Mann D, Minowada J, Gallo RC: Isolation and transmission of human retrovirus (human T-cell leukemia virus). Science 219: 856–859, 1983

    Google Scholar 

  10. Gessain A, Vernant JC, Maurs L, Barin F, Gout O, Calendar A, de The G: Antobodies to human T-lymphotropic virus type I in patiens with tropical spastic paraparesis. Lancet II: 407–410, 1985

    Google Scholar 

  11. Rodgers-Johnson P, St. C. Morgan O, Zaninovic V, Sarin P, Graham DS: HTLV-I and HTLV-III antibodies and tropical spastic paraparesis. Lancet II: 1247–1248, 1985

    Google Scholar 

  12. Bartholomew C, Cleghaorn F, Charles W, Ratan P, Roberts L, Maharaj K, Janke N, Daisley H, Hanchard B, Blattner W: HTLV-I and tropical spastic paraparesis. Lancet II: 99–100, 1986

    Google Scholar 

  13. Osame M, Usuku K, Izumo S, Ijichi N, Amitani H, Igata A, Matsumoto M, Tara M: HTLV-I associated myelopathy, a new clinical entity. Lancet I: 1031–1032, 1986

    Google Scholar 

  14. Ito Y: The epidemiology of human T-cell leukemia/lymphoma virus. Curr Top Microbiol Immunol 115: 99–112, 1985

    Google Scholar 

  15. Nagy K, Clapham P, Cheingsong-Popov R, Weiss R: Human T-cell leukemia virus type I: induction of syncytia and inhibition by patients sera. Int J Cancer 32: 321–328, 1983

    Google Scholar 

  16. Ho DD, Rota TR, Hirsch MS: Infection of human endothelial cells by human T-lymphotropic virus type I. Proc Natl Acad Sci USA 81: 7588–7590, 1984

    Google Scholar 

  17. Hoxie JA, Matthews DM, Cines DB: Infection of human endothelial cells by human T-cell leukemia virus type I. Proc Natl Acad Sci USA 81: 7591–7595, 1984

    Google Scholar 

  18. Rosen CA, Sodroski JG, Haseltine WA: Location of cisacting regulatory sequences in the human T-cell leukemia virus type I long terminal repeat. Proc Natl Acad Sci USA 82: 6502–6506, 1985

    Google Scholar 

  19. Sodroski JG, Rosen CA, Haseltine WA: Trans-acting transcriptional transactivation of the long terminal repeat of human T-lymphotropic viruses in infected cells. Science 225: 381–385, 1984

    Google Scholar 

  20. Cann AJ, Rosenblatt JD, Wachsman W, Shaw NP, Chen ISY: Identification of the gene responsible for human T-cell leukemia virus transcriptional regulation. Nature 318: 571–574, 1985

    Google Scholar 

  21. Felber BK, Paskalis H, Kleinman-Ewing C, Wong-Staal F, Pavlakis GN: The pX protein of HTLV-I is a transcriptional activator of its long terminal repeats. Science 229: 675–679, 1985

    Google Scholar 

  22. Fujisawa J, Seiki M, Kiyokawa T, Yoshida M: Functional activation of the long terminal repeat of human T-cell Leukemia virus type I by a trans acting factor. Proc Natl Acad Sci USA 82: 2277–2281, 1985

    Google Scholar 

  23. Greene WC, Leonard WJ, Wano Y, Svetlik PB, Peffer NJ, Sodroski JG, Rosen CA, Goh WC, Haseltine WA: Transactivator gene of HTLV-II induces IL-2 receptor and IL-2 cellular gene expression. Science 232: 877–880, 1986

    Google Scholar 

  24. Maruyama M, Shibuya H, Harada H, Hatakeyama M, Seiki M, Fujita T, Inoue J, Yoshida M, Taniguchi T: Evidence for aberrant activation of the interleukin-2 autocrine loop by HTLV-I encoded p40x and T3/Ti complex triggering. Cell 48: 343–350, 1987

    Google Scholar 

  25. Nerenberg M, Hinrichs SH, Reynolds RK, Khoury G, Jay G: The tat gene of human T-lymphotropic virus type 1 induces mesenchymal tumors in transgenic mice. Science 237: 1324–1329, 1987

    Google Scholar 

  26. Hinrichs SH, Nerenberg M, Reynolds RK, Khoury G, Jay G: A transgenic mouse model for human neurofibromatosis. Science 237: 1340–1343, 1987

    Google Scholar 

  27. Rubenstein A: Neurofibromatosis: a review of the clinical problem. Ann N Y Acad Sci 486: 1–13, 1986

    Google Scholar 

  28. Erlandson RA: Peripheral nerve sheath tumors. Ultrastruct Pathol 9: 113–129, 1985

    Google Scholar 

  29. Martuza RL, MacLaughlin DT, Ojemann RG: Specific estradiol binding in schwannomas, meningiomas, and neurofibromas. Neurosurgery 9: 665–761, 1981

    Google Scholar 

  30. Riccardi VM, Eichner JE (eds) Neurofibromatosis. Johns Hopkins Univ. Press, Baltimore, MD. 1986

    Google Scholar 

  31. Fauci AS: The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science 239: 617–622, 1988

    Google Scholar 

  32. Dalgleish AG, Beverley PCL, Clapham PR, Crawford DH, Greaves MF, Weiss RA: The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 32: 763–767, 1984

    Google Scholar 

  33. Klatzmann D, Champagne E, Chamaret S, Gruest J, Guetard D, Hercend T, Gluckman J, Montagnier L: T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature 312: 767–768, 1984

    Google Scholar 

  34. Gartner S, Markovits P, Markovitz DM, Kaplan MH, Gallo RC, Popovic M: The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 233: 215–219, 1986

    Google Scholar 

  35. Koenig S, Gendelman HE, Orenstein JM, Dal Canto MC, Pezeshkpour GH, Yungbluth M, Janotta F, Aksamit A, Martin MA, Fauci AS: Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science 233: 1089–1093, 1986

    Google Scholar 

  36. Wiley CA, Schrier RD, Nelson JA, Lampert PW, Oldstone MBA: Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc Natl Acad Sci USA 83: 7089–7093, 1986

    Google Scholar 

  37. Ho DD, Rota TR, Hirsch MS: Infection of monocytes/macrophages by human T lymphocytes with AIDS-associated retrovirus. J Clin Invest 77: 1712–1715, 1986

    Google Scholar 

  38. Niedt GW, Schinella RA: Acquired immunodeficiency syndrome: clinico pathologic study of 56 autopsies. Arch Pathol Lab Med 109: 727–734, 1985

    Google Scholar 

  39. Marmor M, Friedman-Kien AE, Laubenstein L, William DC, D'onofrio S, Dubin N: Risks factors for Kaposi's sarcoma in homosexual men. Lancet I: 1083–1087, 1982

    Google Scholar 

  40. Sodroski J, Rosen C, Wong-Staal F, Salahuddin SZ, Popovic M, Arya S, Gallo RC, Haseltine WA: Trans-acting transcriptional regulation of human T-cell leukemia virus type III long terminal repeat. Science 227: 171–173, 1985

    Google Scholar 

  41. Arya SK, Guo C, Josephs SF, Wong-Staal F: Trans-activator gene of human T-lymphotropic virus type III (HTLV-III). Science 229: 69–73, 1985

    Google Scholar 

  42. Rosen CA, Sodroski JG, Goh WC, Dayton AI, Lippke J, Haseltine WA: Post-transcriptional regulation accounts for the trans-activation of the human T-lymphotropic virus type III. Nature 319: 555–559, 1986

    Google Scholar 

  43. Cullen BR: Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism. Cell 46: 973–982, 1986

    Google Scholar 

  44. Okamoto T, Wong-Staal F: Demonstration of virus-specific transcriptional activator(s) in cells infected with HTLV-III by an in vitro cell-free system. Cell 47: 29–35, 1986

    Google Scholar 

  45. Muesing MA, Smith DH, Capon DJ: Regulation of mRNA accumulation by a human immunodeficiency virus transactivator protein. Cell 48: 691–701, 1987

    Google Scholar 

  46. Vogel J, Hinrichs SH, Reynolds RK, Luciw PA, Jay G: The HIV tat gene induces dermal lesions resembling Kaposi's sarcoma in transgenic mice. Nature, in press

  47. Hoxie JA, Haggarty BS, Rackowski JL, Pillsbury N, Levy JA: Persistent noncytopathic infection of normal human T lymphocytes with AIDS-associated retrovirus. Science 229: 1400–1402, 1985

    Google Scholar 

  48. Folks T, Powell DM, Lightfoote MM, Benn S, Martin MA, Fauci AS: Induction of HTLV-III/LAV from a nonvirus-producing T-cell line: implications for latency. Science 231: 600–602, 1986

    Google Scholar 

  49. Zagury D, Bernard J, Leonard R, Cheyneir R, Feldman M, Sarin P, Gallo RC: Long-term cultures of HTLV-III-infected T cells: a model of cytopathology of T-cell depletion in AIDS. Science 231: 850–853, 1986

    Google Scholar 

  50. Gottlieb GJ, Ackerman AB: Kaposi's sarcoma: an extensively disseminated form in young homosexual men. Hum Pathol 13: 882–892, 1982

    Google Scholar 

  51. Safari B, Johnson KG, Myskowski PL, Koziner B, Yang Y, Cunningham-Ruddles S, Godbold JH, Dupont B: The natural history of Kaposi's sarcoma in the acquired immunodeficiency syndrome. Ann Int Med 103: 744–750, 1985

    Google Scholar 

  52. Safai B, Good RA: Kaposi's sarcoma: a review and recent developments. Clin Bull 10: 62–69, 1980

    Google Scholar 

  53. Curran RC (ed) Color atlas of histopathology. 3rd edition. Oxford Univ. Press, New York. 1985

    Google Scholar 

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Hinrichs, S.H., Vogel, J., Rhim, M.J. et al. Use of transgenic animals to study human retroviruses. Cancer Metast Rev 7, 311–320 (1988). https://doi.org/10.1007/BF00051372

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