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J Virol. 1991 Oct; 65(10): 5471–5476.
PMCID: PMC249039

Polymerase chain reaction analysis of defective human T-cell leukemia virus type I proviral genomes in leukemic cells of patients with adult T-cell leukemia.

Abstract

Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia, and the clonally derived leukemic cells all contain proviral genomes. Polymerase chain reaction with a variety of primers which span the HTLV-I genome was used to determine that a significant fraction of patients (at least 32%) carry deleted viral genomes in their leukemic cells. The pX region of the HTLV-I genome encoding the regulatory genes tax and rex was preferentially retained. The fact that the tax coding region was retained provides supporting evidence that the tax protein contributes to leukemogenesis in vivo. The reasonably high fraction of patients with adult T-cell leukemia carrying deleted genomes in their tumor cells suggests that the deletions have a role in leukemogenesis.

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Selected References

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  • Abbott MA, Poiesz BJ, Byrne BC, Kwok S, Sninsky JJ, Ehrlich GD. Enzymatic gene amplification: qualitative and quantitative methods for detecting proviral DNA amplified in vitro. J Infect Dis. 1988 Dec;158(6):1158–1169. [PubMed]
  • Aldovini A, De Rossi A, Feinberg MB, Wong-Staal F, Franchini G. Molecular analysis of a deletion mutant provirus of type I human T-cell lymphotropic virus: evidence for a doubly spliced x-lor mRNA. Proc Natl Acad Sci U S A. 1986 Jan;83(1):38–42. [PMC free article] [PubMed]
  • Costanzi C, Gillespie D. Fast blots: immobilization of DNA and RNA from cells. Methods Enzymol. 1987;152:582–587. [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]
  • Dokhelar MC, Pickford H, Sodroski J, Haseltine WA. HTLV-I p27rex regulates gag and env protein expression. J Acquir Immune Defic Syndr. 1989;2(5):431–440. [PubMed]
  • Dokhelar MC, Pickford H, Sodroski J, Haseltine WA. The potential for homeostatic regulation of the X region proteins of the human T cell leukemia virus type I. J Acquir Immune Defic Syndr. 1989;2(6):588–594. [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]
  • Franchini G, Wong-Staal F, Gallo RC. Human T-cell leukemia virus (HTLV-I) transcripts in fresh and cultured cells of patients with adult T-cell leukemia. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6207–6211. [PMC free article] [PubMed]
  • Gazdar AF, Carney DN, Bunn PA, Russell EK, Jaffe ES, Schechter GP, Guccion JG. Mitogen requirements for the in vitro propagation of cutaneous T-cell lymphomas. Blood. 1980 Mar;55(3):409–417. [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]
  • Greenberg SJ, Ehrlich GD, Abbott MA, Hurwitz BJ, Waldmann TA, Poiesz BJ. Detection of sequences homologous to human retroviral DNA in multiple sclerosis by gene amplification. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2878–2882. [PMC free article] [PubMed]
  • Haseltine WA, Sodroski J, Patarca R, Briggs D, Perkins D, Wong-Staal F. Structure of 3' terminal region of type II human T lymphotropic virus: evidence for new coding region. Science. 1984 Jul 27;225(4660):419–421. [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]
  • Inoue J, Yoshida M, Seiki M. Transcriptional (p40x) and post-transcriptional (p27x-III) regulators are required for the expression and replication of human T-cell leukemia virus type I genes. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3653–3657. [PMC free article] [PubMed]
  • Jeang KT, Boros I, Brady J, Radonovich M, Khoury G. Characterization of cellular factors that interact with the human T-cell leukemia virus type I p40x-responsive 21-base-pair sequence. J Virol. 1988 Dec;62(12):4499–4509. [PMC free article] [PubMed]
  • Jeang KT, Widen SG, Semmes OJ, 4th, Wilson SH. HTLV-I trans-activator protein, tax, is a trans-repressor of the human beta-polymerase gene. Science. 1990 Mar 2;247(4946):1082–1084. [PubMed]
  • Kwok S, Ehrlich G, Poiesz B, Kalish R, Sninsky JJ. Enzymatic amplification of HTLV-I viral sequences from peripheral blood mononuclear cells and infected tissues. Blood. 1988 Oct;72(4):1117–1123. [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]
  • 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]
  • Nagata K, Ohtani K, Nakamura M, Sugamura K. Activation of endogenous c-fos proto-oncogene expression by human T-cell leukemia virus type I-encoded p40tax protein in the human T-cell line, Jurkat. J Virol. 1989 Aug;63(8):3220–3226. [PMC free article] [PubMed]
  • Okamoto T, Ohno Y, Tsugane S, Watanabe S, Shimoyama M, Tajima K, Miwa M, Shimotohno K. Multi-step carcinogenesis model for adult T-cell leukemia. Jpn J Cancer Res. 1989 Mar;80(3):191–195. [PubMed]
  • Poiesz BJ, Ruscetti FW, Mier JW, Woods AM, Gallo RC. T-cell lines established from human T-lymphocytic neoplasias by direct response to T-cell growth factor. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6815–6819. [PMC free article] [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]
  • Ruben S, Poteat H, Tan TH, Kawakami K, Roeder R, Haseltine W, Rosen CA. Cellular transcription factors and regulation of IL-2 receptor gene expression by HTLV-I tax gene product. Science. 1988 Jul 1;241(4861):89–92. [PubMed]
  • Ruben SM, Perkins A, Rosen CA. Activation of NF-kappa B by the HTLV-I trans-activator protein Tax requires an additional factor present in lymphoid cells. New Biol. 1989 Dec;1(3):275–284. [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, 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]
  • 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]
  • Siomi H, Nosaka T, Saida T, Miwa H, Hinuma Y, Shirakawa S, Miyamoto N, Kondo T, Araki K, Ichimaru M, et al. Two major subgroups of human T-cell leukemia virus-1 in Japan. Virus Genes. 1988 Jul;1(4):377–383. [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 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]
  • Tan TH, Horikoshi M, Roeder RG. Purification and characterization of multiple nuclear factors that bind to the TAX-inducible enhancer within the human T-cell leukemia virus type 1 long terminal repeat. Mol Cell Biol. 1989 Apr;9(4):1733–1745. [PMC free article] [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]
  • Wano Y, Feinberg M, Hosking JB, Bogerd H, Greene WC. Stable expression of the tax gene of type I human T-cell leukemia virus in human T cells activates specific cellular genes involved in growth. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9733–9737. [PMC free article] [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. Recent advances in the molecular biology of HTLV-1: trans-activation of viral and cellular genes. Annu Rev Immunol. 1987;5:541–559. [PubMed]

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