Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Jul;86(14):5620–5624. doi: 10.1073/pnas.86.14.5620

Detection of mRNA for the tax1/rex1 gene of human T-cell leukemia virus type I in fresh peripheral blood mononuclear cells of adult T-cell leukemia patients and viral carriers by using the polymerase chain reaction.

T Kinoshita 1, M Shimoyama 1, K Tobinai 1, M Ito 1, S Ito 1, S Ikeda 1, K Tajima 1, K Shimotohno 1, T Sugimura 1
PMCID: PMC297674  PMID: 2787512

Abstract

Expression of human T-cell leukemia virus type I (HTLV-I) is not detectable by immunofluorescence analysis or RNA blot analysis in most fresh peripheral blood mononuclear cells of patients with adult T-cell leukemia or of asymptomatic HTLV-I carriers. However, in this work, mRNA for the HTLV-I tax1/rex1 genes was detected in fresh peripheral blood mononuclear cells of adult T-cell leukemia patients and asymptomatic HTLV-I carriers by using reverse transcription followed by the polymerase chain reaction. By using fresh peripheral blood mononuclear cells, the expression of tax1/rex1 mRNA was detected in five of the six adult T-cell leukemia patients and four of the eight HTLV-I carriers examined. The amounts of tax1/rex1 mRNA detected corresponded to approximately 10(5) to 10(6) times less than that in the HTLV-I-infected MT-2 cell line. These results indicate that, in some individuals infected with HTLV-I, the provirus in circulating blood cells is transcribed in vivo. Thus the expression of viral antigens in circulating blood cells in vivo is suggested.

Full text

PDF
5620

Images in this article

5622Image
on p.5622
5622Image
on p.5622

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albretsen C., Haukanes B. I., Aasland R., Kleppe K. Optimal conditions for hybridization with oligonucleotides: a study with myc-oncogene DNA probes. Anal Biochem. 1988 Apr;170(1):193–202. doi: 10.1016/0003-2697(88)90108-x. [DOI] [PubMed] [Google Scholar]
  2. Arai N., Nomura D., Villaret D., DeWaal Malefijt R., Seiki M., Yoshida M., Minoshima S., Fukuyama R., Maekawa M., Kudoh J. Complete nucleotide sequence of the chromosomal gene for human IL-4 and its expression. J Immunol. 1989 Jan 1;142(1):274–282. [PubMed] [Google Scholar]
  3. Byrne B. C., Li J. J., Sninsky J., Poiesz B. J. Detection of HIV-1 RNA sequences by in vitro DNA amplification. Nucleic Acids Res. 1988 May 11;16(9):4165–4165. doi: 10.1093/nar/16.9.4165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  5. Cross S. L., Feinberg M. B., Wolf J. B., Holbrook N. J., Wong-Staal F., Leonard W. J. 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. doi: 10.1016/0092-8674(87)90754-9. [DOI] [PubMed] [Google Scholar]
  6. Felber B. K., Paskalis H., Kleinman-Ewing C., Wong-Staal F., Pavlakis G. N. The pX protein of HTLV-I is a transcriptional activator of its long terminal repeats. Science. 1985 Aug 16;229(4714):675–679. doi: 10.1126/science.2992082. [DOI] [PubMed] [Google Scholar]
  7. Franchini G., Wong-Staal F., Gallo R. C. 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. doi: 10.1073/pnas.81.19.6207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fujii M., Sassone-Corsi P., Verma I. M. 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. doi: 10.1073/pnas.85.22.8526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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. doi: 10.1073/pnas.82.8.2277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gallo R., Wong-Staal F., Montagnier L., Haseltine W. A., Yoshida M. HIV/HTLV gene nomenclature. Nature. 1988 Jun 9;333(6173):504–504. doi: 10.1038/333504a0. [DOI] [PubMed] [Google Scholar]
  11. 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] [Google Scholar]
  12. Hinuma Y., Gotoh Y., Sugamura K., Nagata K., Goto T., Nakai M., Kamada N., Matsumoto T., Kinoshita K. A retrovirus associated with human adult T-cell leukemia: in vitro activation. Gan. 1982 Apr;73(2):341–344. [PubMed] [Google Scholar]
  13. Hoshino H., Esumi H., Miwa M., Shimoyama M., Minato K., Tobinai K., Hirose M., Watanabe S., Inada N., Kinoshita K. Establishment and characterization of 10 cell lines derived from patients with adult T-cell leukemia. Proc Natl Acad Sci U S A. 1983 Oct;80(19):6061–6065. doi: 10.1073/pnas.80.19.6061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hoshino H., Shimoyama M., Miwa M., Sugimura T. Detection of lymphocytes producing a human retrovirus associated with adult T-cell leukemia by syncytia induction assay. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7337–7341. doi: 10.1073/pnas.80.23.7337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ikeda M., Fujino R., Matsui T., Yoshida T., Komoda H., Imai J. A new agglutination test for serum antibodies to adult T-cell leukemia virus. Gan. 1984 Oct;75(10):845–848. [PubMed] [Google Scholar]
  16. Inoue J., Watanabe T., Sato M., Oda A., Toyoshima K., Yoshida M., Seiki M. Nucleotide sequence of the protease-coding region in an infectious DNA of simian retrovirus (STLV) of the HTLV-I family. Virology. 1986 Apr 15;150(1):187–195. doi: 10.1016/0042-6822(86)90278-3. [DOI] [PubMed] [Google Scholar]
  17. 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. doi: 10.1073/pnas.84.11.3653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ishibashi K., Hanada S., Hashimoto S. Expression of HTLV-I in serum of HTLV-I-related subjects and the early detection of overt ATL in HTLV-I carriers. J Immunol. 1987 Sep 1;139(5):1509–1513. [PubMed] [Google Scholar]
  19. Kawasaki E. S., Clark S. S., Coyne M. Y., Smith S. D., Champlin R., Witte O. N., McCormick F. P. Diagnosis of chronic myeloid and acute lymphocytic leukemias by detection of leukemia-specific mRNA sequences amplified in vitro. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5698–5702. doi: 10.1073/pnas.85.15.5698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kogan S. C., Doherty M., Gitschier J. An improved method for prenatal diagnosis of genetic diseases by analysis of amplified DNA sequences. Application to hemophilia A. N Engl J Med. 1987 Oct 15;317(16):985–990. doi: 10.1056/NEJM198710153171603. [DOI] [PubMed] [Google Scholar]
  21. 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. doi: 10.1016/0092-8674(87)90437-5. [DOI] [PubMed] [Google Scholar]
  22. Miyatake S., Seiki M., Malefijt R. D., Heike T., Fujisawa J., Takebe Y., Nishida J., Shlomai J., Yokota T., Yoshida M. 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. doi: 10.1093/nar/16.14.6547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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. doi: 10.1038/294770a0. [DOI] [PubMed] [Google Scholar]
  24. Miyoshi I., Yoshimoto S., Ohtsuki Y., Fujishita M., Akagi T., Yoshiki T., Koike T. Adult T-cell leukaemia antigen in renal glomerulus. Lancet. 1983 Apr 2;1(8327):768–769. doi: 10.1016/s0140-6736(83)92060-3. [DOI] [PubMed] [Google Scholar]
  25. Miyoshi I., Yoshimoto S., Taguchi H., Kubonishi I., Fujishita M., Ohtsuki Y., Shiraishi Y., Akagi T. Transformation of rabbit lymphocytes with T-cell leukemia virus. Gan. 1983 Feb;74(1):1–4. [PubMed] [Google Scholar]
  26. Noonan K. E., Roninson I. B. mRNA phenotyping by enzymatic amplification of randomly primed cDNA. Nucleic Acids Res. 1988 Nov 11;16(21):10366–10366. doi: 10.1093/nar/16.21.10366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ohtsu T., Tsugane S., Tobinai K., Shimoyama M., Nanri S., Watanabe S. Prevalence of antibodies to human T-cell leukemia/lymphoma virus type I and human immunodeficiency virus in Japanese immigrant colonies in Bolivia and Bolivian natives. Jpn J Cancer Res. 1987 Dec;78(12):1347–1353. [PubMed] [Google Scholar]
  28. Osame M., Matsumoto M., Usuku K., Izumo S., Ijichi N., Amitani H., Tara M., Igata A. Chronic progressive myelopathy associated with elevated antibodies to human T-lymphotropic virus type I and adult T-cell leukemialike cells. Ann Neurol. 1987 Feb;21(2):117–122. doi: 10.1002/ana.410210203. [DOI] [PubMed] [Google Scholar]
  29. Poiesz B. J., Ruscetti F. W., Gazdar A. F., Bunn P. A., Minna J. D., Gallo R. C. 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. doi: 10.1073/pnas.77.12.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Powell L. M., Wallis S. C., Pease R. J., Edwards Y. H., Knott T. J., Scott J. A novel form of tissue-specific RNA processing produces apolipoprotein-B48 in intestine. Cell. 1987 Sep 11;50(6):831–840. doi: 10.1016/0092-8674(87)90510-1. [DOI] [PubMed] [Google Scholar]
  31. Rappolee D. A., Brenner C. A., Schultz R., Mark D., Werb Z. Developmental expression of PDGF, TGF-alpha, and TGF-beta genes in preimplantation mouse embryos. Science. 1988 Sep 30;241(4874):1823–1825. doi: 10.1126/science.3175624. [DOI] [PubMed] [Google Scholar]
  32. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  33. Saiki R. K., Scharf S., Faloona F., Mullis K. B., Horn G. T., Erlich H. A., Arnheim N. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985 Dec 20;230(4732):1350–1354. doi: 10.1126/science.2999980. [DOI] [PubMed] [Google Scholar]
  34. Schüpbach J., Kalyanaraman V. S., Sarngadharan M. G., Bunn P. A., Blayney D. W., Gallo R. C. Demonstration of viral antigen p24 in circulating immune complexes of two patients with human T-cell leukaemia/lymphoma virus (HTLV) positive lymphoma. Lancet. 1984 Feb 11;1(8372):302–305. doi: 10.1016/s0140-6736(84)90358-1. [DOI] [PubMed] [Google Scholar]
  35. 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. doi: 10.1073/pnas.80.12.3618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. 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. doi: 10.1073/pnas.85.19.7124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. 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. doi: 10.1002/j.1460-2075.1986.tb04247.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Shimoyama M., Kagami Y., Shimotohno K., Miwa M., Minato K., Tobinai K., Suemasu K., Sugimura T. Adult T-cell leukemia/lymphoma not associated with human T-cell leukemia virus type I. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4524–4528. doi: 10.1073/pnas.83.12.4524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Shimoyama M., Minato K., Tobinai K., Nagai M., Setoya T., Takenaka T., Ishihara K., Watanabe S., Hoshino H., Miwa M. Atypical adult T-cell leukemia-lymphoma: diverse clinical manifestations of adult T-cell leukemia-lymphoma. Jpn J Clin Oncol. 1983;13 (Suppl 2):165–187. [PubMed] [Google Scholar]
  40. Siekevitz M., Feinberg M. B., Holbrook N., Wong-Staal F., Greene W. C. 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. doi: 10.1073/pnas.84.15.5389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Sodroski J. G., Rosen C. A., Haseltine W. A. 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. doi: 10.1126/science.6330891. [DOI] [PubMed] [Google Scholar]
  42. Sodroski J., Rosen C., Goh W. C., 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. doi: 10.1126/science.2990028. [DOI] [PubMed] [Google Scholar]
  43. Sugamura K., Fujii M., Kannagi M., Sakitani M., Takeuchi M., Hinuma Y. Cell surface phenotypes and expression of viral antigens of various human cell lines carrying human T-cell leukemia virus. Int J Cancer. 1984 Aug 15;34(2):221–228. doi: 10.1002/ijc.2910340213. [DOI] [PubMed] [Google Scholar]
  44. Tateno M., Kondo N., Itoh T., Chubachi T., Togashi T., Yoshiki T. Rat lymphoid cell lines with human T cell leukemia virus production. I. Biological and serological characterization. J Exp Med. 1984 Apr 1;159(4):1105–1116. doi: 10.1084/jem.159.4.1105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Tochikura T., Iwahashi M., Matsumoto T., Koyanagi Y., Hinuma Y., Yamamoto N. Effect of human serum anti-HTLV antibodies on viral antigen induction in vitro cultured peripheral lymphocytes from adult T-cell leukemia patients and healthy virus carriers. Int J Cancer. 1985 Jul 15;36(1):1–7. doi: 10.1002/ijc.2910360102. [DOI] [PubMed] [Google Scholar]
  46. Todd J. A., Bell J. I., McDevitt H. O. HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature. 1987 Oct 15;329(6140):599–604. doi: 10.1038/329599a0. [DOI] [PubMed] [Google Scholar]
  47. 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] [Google Scholar]
  48. Yoshida M. Expression of the HTLV-1 genome and its association with a unique T-cell malignancy. Biochim Biophys Acta. 1987 Jul 8;907(2):145–161. doi: 10.1016/0304-419x(87)90003-5. [DOI] [PubMed] [Google Scholar]
  49. 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. doi: 10.1073/pnas.79.6.2031. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES