Expression of HTLV-1 in Transgenic Mice

  • Michael I. Nerenberg
  • Gilbert Jay


Transgenic technology has been used to determine the biological effects of individual viral gene products in an intact organism. This approach may minimize much of the pathogenic complexity seen during natural infection of animals as a result of variable targeting, differential expression of antigens, and the complicating effects of attack by the immune system. Specific transcriptional promoters may be chosen to target gene expression to certain tissues of interest or to broaden the repertoire of tissue-specific expression beyond what is commonly seen in natural infections. This technology may also be used to derive models of human disease and to create useful cellular and biochemical reagents for the investigation of viral pathogenesis.


Leukemia Neurol Peri Nism Rosen 


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  1. 1.
    Gallo RC (1986) The first human retrovirus. Sci Amer 255: 88–98PubMedCrossRefGoogle Scholar
  2. 2.
    Williams AE, Fang CT, Slamon DJ, Poiesz BJ, Sandler SG, Darr WF, Shulman G, McGowan EI, Douglas DK, Bowman RJ, Peetoom F, Kleinman SH, Lenes B, Dodd RY (1988) Seroprevalence and epidemiological correlates of HTLV-I infection in U.S. blood donors. Science 240: 643–646PubMedCrossRefGoogle Scholar
  3. 3.
    Ito Y (1985) The epidemiology of human T-cell leukemia/lymphoma virus. Curr Top Microbiol Immunol 115: 99–112PubMedCrossRefGoogle Scholar
  4. 4.
    Gessain A, Vernant JC, Maurs L, Barin F, Gout O, Calendar A, DeThe G (1985) Antibodies to human T-lymphotropic virus type I in patients with tropical spastic paraparesis. Lancet ii: 407–409CrossRefGoogle Scholar
  5. 5.
    Rodgers-Johnson P, St O, Morgan C, Zaninovic V, Sarin P, Graham DS (1985) HTLV-I and HTLV-II antibodies and tropical spastic paraparesis. Lancet ii: 1247–1248CrossRefGoogle Scholar
  6. 6.
    Bartholomew C, Cleghaorn F, Charles W, Ratan P, Roberts L, Maharaj K, Janke N, Daisley H, Hanchard B, Blattner W (1986) HTLV-1 and tropical spastic paraparesis. Lancet ii: 99–100CrossRefGoogle Scholar
  7. 7.
    Osame M, Usuku K, Izumo S, Ijichi N, Amitani H, Igata A, Matsumoto M, Tara M (1986) HTLV-I associated myelopathy, a new clinical entity. Lancet ii: 1032Google Scholar
  8. 8.
    Jacobson S, Raine CS, Mingioli ES, McFarlin DE (1988) Isolation of an HTLV-1-like retrovirus from patients with tropical spastic paraparesis. Nature 331: 540–543PubMedCrossRefGoogle Scholar
  9. 9.
    Sodroski JG, Rosen CA, Haseltine WA (1984) Trans-acting transcriptional transactivation of the long terminal repeat of human T-lymphotropic viruses in infected cells. Science 225: 381–385PubMedCrossRefGoogle Scholar
  10. 10.
    Fujisawa J, Seiki M, Kiyokawa T, Yoshida M (1985) 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: 2277–2281PubMedCrossRefGoogle Scholar
  11. 11.
    Felber BK, Paskalis H, Kleinman-Ewing C, Wong-Staal F, Pavlakis GN (1985) The pX protein of HTLV-I is a transcriptional activator of its long terminal repeats. Science 229: 675–679PubMedCrossRefGoogle Scholar
  12. 12.
    Cann AJ, Rosenblatt JD, Wachsman W, Shaw NP, Chen ISY (1985) Identification of the gene responsible for human T-cell leukemia virus transcriptional regulation. Nature 318: 571–574PubMedCrossRefGoogle Scholar
  13. 13.
    Greene WC, Leonard WJ, Wano Y, Svetlik PB, Peffer NK, Sodroski JG, Rosen CA, Goh WC, Haseltine WC (1986) Trans-activator gene of HTLV-I1 induces IL-2 receptor and IL-2 cellular gene expression. Science 232: 877–880PubMedCrossRefGoogle Scholar
  14. 14.
    Maruyama M, Shibuya H, Harada H, Hatakeyama M, Seiki M, Fujita T, Inoue J, Yoshida M, Taniguchi T (1987) Evidence for aberrant activation of the interleukin-2 autocrine loop by HTLV-1 encoded p40 and T3/Ti complex triggering. Cell 48: 343–350PubMedCrossRefGoogle Scholar
  15. 15.
    Nagy K, Clapham P, Cheingsong-Popov R, Weiss R (1983) Human T-cell leukemia virus type I: Induction of syncytia and inhibition by patients sera. Int J Cancer 32: 321–328PubMedCrossRefGoogle Scholar
  16. 16.
    Ho DD, Rota TR, Hirsch MS (1984) Infection of human endothelial cells by human T-lymphotropic virus type I. Proc Natl Acad Sci USA 81: 7588–7590PubMedCrossRefGoogle Scholar
  17. 17.
    Hoxie JA, Matthews DM, Cines DB (1984) Infection of human endothelial cells by human T-cell leukemia virus type I. Proc Natl Acad Sci USA 81: 7591–7595PubMedCrossRefGoogle Scholar
  18. 18.
    Nerenberg MI, Hinrichs SH, Reynolds RK, Khoury G, Jay G (1987) The tat gene of human T lymphotropic virus type I induces mesenchymal tumors in transgenic mice. Science 237: 1324–1329PubMedCrossRefGoogle Scholar
  19. 19.
    Hinrichs SH, Nerenberg M, Reynolds RK, Khoury G, Jay G (1987) A transgenic mouse model for human neurofibromatosis. Science 237: 1340–1343PubMedCrossRefGoogle Scholar
  20. 20.
    Nerenberg Ml, Wiley CA (1988) The HTLV-1 tat protein induces tissue specific disorders of neoplasia and atrophy in transgenic mice (manuscript submitted)Google Scholar
  21. 21.
    Wiley CA, Nerenberg M, Cros D, Soto-Aguilar MC (1989) HTLV-1 Polymyositis. N Engl J Med (in press)Google Scholar
  22. 22.
    Mora CA, Garruto RM, Brown P, Guiroy D, Morgan OS, Rodgers-Johnson P, Ceroni M, Yanagihara R, Goldfarb LG, Gibbs CF Jr, et al (1988) Seroprevalence of antibodies to HTLV-1 in patients with chronic neurological disorders other than tropical spastic paraparesis. Ann Neurol 23: S192–S195CrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1989

Authors and Affiliations

  • Michael I. Nerenberg
  • Gilbert Jay

There are no affiliations available

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