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J Virol. Jul 1992; 66(7): 4570–4575.
PMCID: PMC241270

Role of human T-cell leukemia virus type 1 X region proteins in immortalization of primary human lymphocytes in culture.

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) immortalizes human CD4+ T lymphocytes in culture. Previous studies show that in the context of a herpesvirus saimiri vector, the sequence of the X region at the 3' end of the HTLV-1 genome is also capable of immortalizing CD4+ lymphocytes in the absence of HTLV-1 structural proteins. The X region of HTLV-1 encodes two trans-acting viral proteins, the 42-kDa Tax protein and the 27-kDa Rex protein. Infection of human cord blood cells with herpesvirus saimiri recombinants which contain HTLV-1 X region sequences defective for expression of tax, rex, or both tax and rex demonstrates that tax function is necessary and sufficient for immortalization of primary human CD4+ cord blood lymphocytes in culture in the context of the herpesvirus saimiri vector.

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Selected References

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  • Ahmed YF, Gilmartin GM, Hanly SM, Nevins JR, Greene WC. The HTLV-I Rex response element mediates a novel form of mRNA polyadenylation. Cell. 1991 Feb 22;64(4):727–737. [PubMed]
  • Alt M, Fleckenstein B, Grassmann R. A pair of selectable herpesvirus vectors for simultaneous gene expression in human lymphoid cells. Gene. 1991 Jun 30;102(2):265–269. [PubMed]
  • Ballaun C, Farrington GK, Dobrovnik M, Rusche J, Hauber J, Böhnlein E. Functional analysis of human T-cell leukemia virus type I rex-response element: direct RNA binding of Rex protein correlates with in vivo activity. J Virol. 1991 Aug;65(8):4408–4413. [PMC free article] [PubMed]
  • Bogerd HP, Huckaby GL, Ahmed YF, Hanly SM, Greene WC. The type I human T-cell leukemia virus (HTLV-I) Rex trans-activator binds directly to the HTLV-I Rex and the type 1 human immunodeficiency virus Rev RNA response elements. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5704–5708. [PMC free article] [PubMed]
  • Böhnlein E, Siekevitz M, Ballard DW, Lowenthal JW, Rimsky L, Bogérd H, Hoffman J, Wano Y, Franza BR, Greene WC. Stimulation of the human immunodeficiency virus type 1 enhancer by the human T-cell leukemia virus type I tax gene product involves the action of inducible cellular proteins. J Virol. 1989 Apr;63(4):1578–1586. [PMC free article] [PubMed]
  • Cann AJ, Rosenblatt JD, Wachsman W, Shah NP, Chen IS. Identification of the gene responsible for human T-cell leukaemia virus transcriptional regulation. Nature. 1985 Dec 12;318(6046):571–574. [PubMed]
  • Celander D, Haseltine WA. Tissue-specific transcription preference as a determinant of cell tropism and leukaemogenic potential of murine retroviruses. Nature. 1984 Nov 8;312(5990):159–162. [PubMed]
  • Cross SL, Feinberg MB, Wolf JB, Holbrook NJ, Wong-Staal F, Leonard WJ. Regulation of the human interleukin-2 receptor alpha chain promoter: activation of a nonfunctional promoter by the transactivator gene of HTLV-I. Cell. 1987 Apr 10;49(1):47–56. [PubMed]
  • Desrosiers RC, Burghoff RL, Bakker A, Kamine J. Construction of replication-competent Herpesvirus saimiri deletion mutants. J Virol. 1984 Feb;49(2):343–348. [PMC free article] [PubMed]
  • Desrosiers RC, Silva DP, Waldron LM, Letvin NL. Nononcogenic deletion mutants of herpesvirus saimiri are defective for in vitro immortalization. J Virol. 1986 Feb;57(2):701–705. [PMC free article] [PubMed]
  • Fujii M, Niki T, Mori T, Matsuda T, Matsui M, Nomura N, Seiki M. HTLV-1 Tax induces expression of various immediate early serum responsive genes. Oncogene. 1991 Jun;6(6):1023–1029. [PubMed]
  • Fujii M, Sassone-Corsi P, Verma IM. c-fos promoter trans-activation by the tax1 protein of human T-cell leukemia virus type I. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8526–8530. [PMC free article] [PubMed]
  • Furuta Y, Aizawa S, Suda Y, Ikawa Y, Kishimoto H, Asano Y, Tada T, Hikikoshi A, Yoshida M, Seiki M. Thymic atrophy characteristic in transgenic mice that harbor pX genes of human T-cell leukemia virus type I. J Virol. 1989 Jul;63(7):3185–3189. [PMC free article] [PubMed]
  • Gardella T, Medveczky P, Sairenji T, Mulder C. Detection of circular and linear herpesvirus DNA molecules in mammalian cells by gel electrophoresis. J Virol. 1984 Apr;50(1):248–254. [PMC free article] [PubMed]
  • Gessain A, Barin F, Vernant JC, Gout O, Maurs L, Calender A, de Thé G. Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet. 1985 Aug 24;2(8452):407–410. [PubMed]
  • Grassmann R, Berchtold S, Aepinus C, Ballaun C, Boehnlein E, Fleckenstein B. In vitro binding of human T-cell leukemia virus rex proteins to the rex-response element of viral transcripts. J Virol. 1991 Jul;65(7):3721–3727. [PMC free article] [PubMed]
  • Grassmann R, Dengler C, Müller-Fleckenstein I, Fleckenstein B, McGuire K, Dokhelar MC, Sodroski JG, Haseltine WA. Transformation to continuous growth of primary human T lymphocytes by human T-cell leukemia virus type I X-region genes transduced by a Herpesvirus saimiri vector. Proc Natl Acad Sci U S A. 1989 May;86(9):3351–3355. [PMC free article] [PubMed]
  • Grassmann R, Fleckenstein B. Selectable recombinant herpesvirus saimiri is capable of persisting in a human T-cell line. J Virol. 1989 Apr;63(4):1818–1821. [PMC free article] [PubMed]
  • Hanly SM, Rimsky LT, Malim MH, Kim JH, Hauber J, Duc Dodon M, Le SY, Maizel JV, Cullen BR, Greene WC. Comparative analysis of the HTLV-I Rex and HIV-1 Rev trans-regulatory proteins and their RNA response elements. Genes Dev. 1989 Oct;3(10):1534–1544. [PubMed]
  • Hinrichs SH, Nerenberg M, Reynolds RK, Khoury G, Jay G. A transgenic mouse model for human neurofibromatosis. Science. 1987 Sep 11;237(4820):1340–1343. [PubMed]
  • Inoue J, Seiki M, Taniguchi T, Tsuru S, Yoshida M. Induction of interleukin 2 receptor gene expression by p40x encoded by human T-cell leukemia virus type 1. EMBO J. 1986 Nov;5(11):2883–2888. [PMC free article] [PubMed]
  • Jacobson S, Raine CS, Mingioli ES, McFarlin DE. Isolation of an HTLV-1-like retrovirus from patients with tropical spastic paraparesis. Nature. 1988 Feb 11;331(6156):540–543. [PubMed]
  • Kanamori H, Suzuki N, Siomi H, Nosaka T, Sato A, Sabe H, Hatanaka M, Honjo T. HTLV-1 p27rex stabilizes human interleukin-2 receptor alpha chain mRNA. EMBO J. 1990 Dec;9(12):4161–4166. [PMC free article] [PubMed]
  • Kim SJ, Kehrl JH, Burton J, Tendler CL, Jeang KT, Danielpour D, Thevenin C, Kim KY, Sporn MB, Roberts AB. Transactivation of the transforming growth factor beta 1 (TGF-beta 1) gene by human T lymphotropic virus type 1 tax: a potential mechanism for the increased production of TGF-beta 1 in adult T cell leukemia. J Exp Med. 1990 Jul 1;172(1):121–129. [PMC free article] [PubMed]
  • Marriott SJ, Lindholm PF, Reid RL, Brady JN. Soluble HTLV-I Tax1 protein stimulates proliferation of human peripheral blood lymphocytes. New Biol. 1991 Jul;3(7):678–686. [PubMed]
  • 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-1-encoded p40x and T3/Ti complex triggering. Cell. 1987 Jan 30;48(2):343–350. [PubMed]
  • Miyatake S, Seiki M, Malefijt RD, Heike T, Fujisawa J, Takebe Y, Nishida J, Shlomai J, Yokota T, Yoshida M, et al. Activation of T cell-derived lymphokine genes in T cells and fibroblasts: effects of human T cell leukemia virus type I p40x protein and bovine papilloma virus encoded E2 protein. Nucleic Acids Res. 1988 Jul 25;16(14A):6547–6566. [PMC free article] [PubMed]
  • Miyoshi I, Kubonishi I, Yoshimoto S, Akagi T, Ohtsuki Y, Shiraishi Y, Nagata K, Hinuma Y. Type C virus particles in a cord T-cell line derived by co-cultivating normal human cord leukocytes and human leukaemic T cells. Nature. 1981 Dec 24;294(5843):770–771. [PubMed]
  • Nagashima K, Yoshida M, Seiki M. A single species of pX mRNA of human T-cell leukemia virus type I encodes trans-activator p40x and two other phosphoproteins. J Virol. 1986 Nov;60(2):394–399. [PMC free article] [PubMed]
  • Niitsu Y, Urushizaki Y, Koshida Y, Terui K, Mahara K, Kohgo Y, Urushizaki I. Expression of TGF-beta gene in adult T cell leukemia. Blood. 1988 Jan;71(1):263–266. [PubMed]
  • 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. 1987 Sep 11;237(4820):1324–1329. [PubMed]
  • Nerenberg MI, Minor T, Price J, Ernst DN, Shinohara T, Schwarz H. Transgenic thymocytes are refractory to transformation by the human T-cell leukemia virus type I tax gene. J Virol. 1991 Jun;65(6):3349–3353. [PMC free article] [PubMed]
  • 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. 1986 May 3;1(8488):1031–1032. [PubMed]
  • Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415–7419. [PMC free article] [PubMed]
  • Poiesz 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 Sézary T-cell leukaemia. Nature. 1981 Nov 19;294(5838):268–271. [PubMed]
  • Popovic M, Lange-Wantzin G, Sarin PS, Mann D, Gallo RC. Transformation of human umbilical cord blood T cells by human T-cell leukemia/lymphoma virus. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5402–5406. [PMC free article] [PubMed]
  • Pozzatti R, Vogel J, Jay G. The human T-lymphotropic virus type I tax gene can cooperate with the ras oncogene to induce neoplastic transformation of cells. Mol Cell Biol. 1990 Jan;10(1):413–417. [PMC free article] [PubMed]
  • Seiki M, Eddy R, Shows TB, Yoshida M. Nonspecific integration of the HTLV provirus genome into adult T-cell leukaemia cells. Nature. 1984 Jun 14;309(5969):640–642. [PubMed]
  • Seiki M, Hattori S, Hirayama Y, Yoshida M. Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3618–3622. [PMC free article] [PubMed]
  • Seiki M, Inoue J, Hidaka M, Yoshida M. Two cis-acting elements responsible for posttranscriptional trans-regulation of gene expression of human T-cell leukemia virus type I. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7124–7128. [PMC free article] [PubMed]
  • Seiki M, Inoue J, Takeda T, Yoshida M. Direct evidence that p40x of human T-cell leukemia virus type I is a trans-acting transcriptional activator. EMBO J. 1986 Mar;5(3):561–565. [PMC free article] [PubMed]
  • Siekevitz M, Feinberg MB, Holbrook N, Wong-Staal F, Greene WC. Activation of interleukin 2 and interleukin 2 receptor (Tac) promoter expression by the trans-activator (tat) gene product of human T-cell leukemia virus, type I. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5389–5393. [PMC free article] [PubMed]
  • Simmer B, Alt M, Buckreus I, Berthold S, Fleckenstein B, Platzer E, Grassmann R. Persistence of selectable herpesvirus saimiri in various human haematopoietic and epithelial cell lines. J Gen Virol. 1991 Aug;72(Pt 8):1953–1958. [PubMed]
  • Smith MR, Greene WC. Identification of HTLV-I tax trans-activator mutants exhibiting novel transcriptional phenotypes. Genes Dev. 1990 Nov;4(11):1875–1885. [PubMed]
  • Sodroski JG, Rosen CA, Haseltine WA. Trans-acting transcriptional activation of the long terminal repeat of human T lymphotropic viruses in infected cells. Science. 1984 Jul 27;225(4660):381–385. [PubMed]
  • Tanaka A, Takahashi C, Yamaoka S, Nosaka T, Maki M, Hatanaka M. Oncogenic transformation by the tax gene of human T-cell leukemia virus type I in vitro. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1071–1075. [PMC free article] [PubMed]
  • Toyoshima H, Itoh M, Inoue J, Seiki M, Takaku F, Yoshida M. Secondary structure of the human T-cell leukemia virus type 1 rex-responsive element is essential for rex regulation of RNA processing and transport of unspliced RNAs. J Virol. 1990 Jun;64(6):2825–2832. [PMC free article] [PubMed]
  • Tschachler E, Robert-Guroff M, Gallo RC, Reitz MS., Jr Human T-lymphotropic virus I-infected T cells constitutively express lymphotoxin in vitro. Blood. 1989 Jan;73(1):194–201. [PubMed]
  • Wright JJ, Gunter KC, Mitsuya H, Irving SG, Kelly K, Siebenlist U. Expression of a zinc finger gene in HTLV-I- and HTLV-II-transformed cells. Science. 1990 May 4;248(4955):588–591. [PubMed]
  • Yamamoto N, Okada M, Koyanagi Y, Kannagi M, Hinuma Y. Transformation of human leukocytes by cocultivation with an adult T cell leukemia virus producer cell line. Science. 1982 Aug 20;217(4561):737–739. [PubMed]
  • Yoshida M, Miyoshi I, Hinuma Y. Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease. Proc Natl Acad Sci U S A. 1982 Mar;79(6):2031–2035. [PMC free article] [PubMed]

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