• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of embojLink to Publisher's site
EMBO J. Nov 1986; 5(11): 2883–2888.
PMCID: PMC1167238

Induction of interleukin 2 receptor gene expression by p40x encoded by human T-cell leukemia virus type 1.

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is an etiologic agent of adult T-cell leukemia (ATL). A viral product, p40x, encoded by the pX sequence of HTLV-1 is a trans-acting transcriptional activator of the long terminal repeat (LTR) and has been suspected of involvement in leukemogenesis, activating the cellular genes. The cellular interleukin-2 (IL-2) and its receptor (IL-2R), the latter of which is expressed on ATL leukemic cells, were shown to be transiently induced by transfection of plasmid pMTPX expressing pX in two T-cell lines, Jurkat and HSB-2, but not in other human T- or B-cell lines. The cell type specificity of IL-2R induction by pX expression was the same as that by phytohaemagglutinin/phorbol ester activation, indicating the requirement for some specific cellular factors or a certain state of cellular differentiation. Induction of IL-2 and IL-2R at mRNA level was also demonstrated in transfected cells. Transfections with mutants of pMTPX in which the open reading frames for p40x, p27x-III and p21x-III were inactivated indicated that p40x alone was sufficient for induction of the IL-2R in inducible cells. This induction of the IL-2R by p40x of HTLV-1 may contribute to preferential proliferation of HTLV-1 infected cells at an early stage of ATL development and eventually increase the number of putative target cells for malignant transformation.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Berger SL, Birkenmeier CS. Inhibition of intractable nucleases with ribonucleoside--vanadyl complexes: isolation of messenger ribonucleic acid from resting lymphocytes. Biochemistry. 1979 Nov 13;18(23):5143–5149. [PubMed]
  • Breathnach R, Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. [PubMed]
  • Chen IS, Slamon DJ, Rosenblatt JD, Shah NP, Quan SG, Wachsman W. The x gene is essential for HTLV replication. Science. 1985 Jul 5;229(4708):54–58. [PubMed]
  • Depper JM, Leonard WJ, Krönke M, Waldmann TA, Greene WC. Augmented T cell growth factor receptor expression in HTLV-1-infected human leukemic T cells. J Immunol. 1984 Oct;133(4):1691–1695. [PubMed]
  • 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. 1985 Aug 16;229(4714):675–679. [PubMed]
  • 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 U S A. 1985 Apr;82(8):2277–2281. [PMC free article] [PubMed]
  • Fujisawa J, Seiki M, Sato M, Yoshida M. A transcriptional enhancer sequence of HTLV-I is responsible for trans-activation mediated by p40 chi HTLV-I. EMBO J. 1986 Apr;5(4):713–718. [PMC free article] [PubMed]
  • Greene WC, Robb RJ, Depper JM, Leonard WJ, Drogula C, Svetlik PB, Wong-Staal F, Gallo RC, Waldmann TA. Phorbol diester induces expression of Tac antigen on human acute T lymphocytic leukemic cells. J Immunol. 1984 Aug;133(2):1042–1047. [PubMed]
  • Greene WC, Leonard WJ, Wano Y, Svetlik PB, Peffer NJ, Sodroski JG, Rosen CA, Goh WC, Haseltine WA. Trans-activator gene of HTLV-II induces IL-2 receptor and IL-2 cellular gene expression. Science. 1986 May 16;232(4752):877–880. [PubMed]
  • Hattori T, Uchiyama T, Toibana T, Takatsuki K, Uchino H. Surface phenotype of Japanese adult T-cell leukemia cells characterized by monoclonal antibodies. Blood. 1981 Sep;58(3):645–647. [PubMed]
  • Hinuma Y, Nagata K, Hanaoka M, Nakai M, Matsumoto T, Kinoshita KI, Shirakawa S, Miyoshi I. Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6476–6480. [PMC free article] [PubMed]
  • Kiyokawa T, Seiki M, Imagawa K, Shimizu F, Yoshida M. Identification of a protein (p40x) encoded by a unique sequence pX of human T-cell leukemia virus type I. Gann. 1984 Sep;75(9):747–751. [PubMed]
  • Kiyokawa T, Seiki M, Iwashita S, Imagawa K, Shimizu F, Yoshida M. p27x-III and p21x-III, proteins encoded by the pX sequence of human T-cell leukemia virus type I. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8359–8363. [PMC free article] [PubMed]
  • Lee TH, Coligan JE, Sodroski JG, Haseltine WA, Salahuddin SZ, Wong-Staal F, Gallo RC, Essex M. Antigens encoded by the 3'-terminal region of human T-cell leukemia virus: evidence for a functional gene. Science. 1984 Oct 5;226(4670):57–61. [PubMed]
  • Miwa M, Shimotohno K, Hoshino H, Fujino M, Sugimura T. Detection of pX proteins in human T-cell leukemia virus (HTLV)-infected cells by using antibody against peptide deduced from sequences of X-IV DNA of HTLV-I and Xc DNA of HTLV-II proviruses. Gann. 1984 Sep;75(9):752–755. [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]
  • 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]
  • 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]
  • 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, 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, Inoue J, Takeda T, Hikikoshi A, Sato M, Yoshida M. The p40x of human T-cell leukemia virus type I is a trans-acting activator of viral gene transcription. Jpn J Cancer Res. 1985 Dec;76(12):1127–1131. [PubMed]
  • Seiki M, Hikikoshi A, Taniguchi T, Yoshida M. Expression of the pX gene of HTLV-I: general splicing mechanism in the HTLV family. Science. 1985 Jun 28;228(4707):1532–1534. [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]
  • Slamon DJ, Shimotohno K, Cline MJ, Golde DW, Chen IS. Identification of the putative transforming protein of the human T-cell leukemia viruses HTLV-I and HTLV-II. Science. 1984 Oct 5;226(4670):61–65. [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]
  • Sodroski J, Rosen C, Goh WC, Haseltine W. A transcriptional activator protein encoded by the x-lor region of the human T-cell leukemia virus. Science. 1985 Jun 21;228(4706):1430–1434. [PubMed]
  • Sugano S, Yamaguchi N. Two classes of transformation-deficient, immortalization-positive simian virus 40 mutants constructed by making three-base insertions in the T antigen gene. J Virol. 1984 Dec;52(3):884–891. [PMC free article] [PubMed]
  • Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H. Adult T-cell leukemia: clinical and hematologic features of 16 cases. Blood. 1977 Sep;50(3):481–492. [PubMed]
  • Uchiyama T, Broder S, Waldmann TA. A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac (+) cells. J Immunol. 1981 Apr;126(4):1393–1397. [PubMed]
  • Urdal DL, March CJ, Gillis S, Larsen A, Dower SK. Purification and chemical characterization of the receptor for interleukin 2 from activated human T lymphocytes and from a human T-cell lymphoma cell line. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6481–6485. [PMC free article] [PubMed]
  • Wong-Staal F, Hahn B, Manzari V, Colombini S, Franchini G, Gelmann EP, Gallo RC. A survey of human leukaemias for sequences of a human retrovirus. Nature. 1983 Apr 14;302(5909):626–628. [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]
  • Yoshida M, Seiki M, Yamaguchi K, Takatsuki K. Monoclonal integration of human T-cell leukemia provirus in all primary tumors of adult T-cell leukemia suggests causative role of human T-cell leukemia virus in the disease. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2534–2537. [PMC free article] [PubMed]

Articles from The EMBO Journal are provided here courtesy of The European Molecular Biology Organization

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...