Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1994 May;96(2):193–201. doi: 10.1111/j.1365-2249.1994.tb06541.x

Expression of human T lymphotropic virus type 1 (HTLV-1) tax/rex gene in fresh bronchoalveolar lavage cells of HTLV-1-infected individuals.

Y Higashiyama 1, S Katamine 1, S Kohno 1, H Mukae 1, S Hino 1, T Miyamoto 1, K Hara 1
PMCID: PMC1534900  PMID: 7910532

Abstract

Accumulating evidence has suggested the involvement of HTLV-1 in the inflammatory lesions of various organs, including the lung. However, the causal relationship between HTLV-1 and inflammatory responses in the organs remains to be elucidated. In order to evaluate the expression of HTLV-1 and its effects in the lung, we examined the expression of mRNA for the HTLV-1 tax/rex gene in fresh bronchoalveolar lavage cells (BALC) and peripheral blood mononuclear cells (PBMC) of 23 seropositive individuals, including six patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), by use of an improved method of reverse transcription-polymerase chain reaction (RT-PCR). The tax/rex mRNA was more frequently detected in BALC than in PBMC. All the HAM/TSP patients and eight of 17 carriers without neurological symptoms showed the expression of tax/rex mRNA in the BALC. IgM class antibodies to HTLV-1 were preferentially detected in sera of the tax/rex mRNA-positive individuals. The detection of tax/rex mRNA correlated closely with the presence of lymphocytosis accompanied by an elevated proportion of IL-2 receptor-bearing T cells in the BALC. Our findings indicate the crucial role of viral expression in the inflammatory response in the lung in HTLV-1-infected individuals.

Full text

PDF
193

Images in this article

197Fig. 1
on p.197
198Fig. 3
on p.198

Selected References

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

  1. 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]
  2. Couderc L. J., Caubarrere I., Venet A., Magdeleine J., Jouanelle A., Danon F., Buisson G., Vernant J. C. Bronchoalveolar lymphocytosis in patients with tropical spastic paraparesis associated with human T-cell lymphotropic virus type 1 (HTLV-1). Clinical, immunologic, and cytologic studies. Ann Intern Med. 1988 Oct 15;109(8):625–628. doi: 10.7326/0003-4819-109-8-625. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Eguchi K., Matsuoka N., Ida H., Nakashima M., Sakai M., Sakito S., Kawakami A., Terada K., Shimada H., Kawabe Y. Primary Sjögren's syndrome with antibodies to HTLV-I: clinical and laboratory features. Ann Rheum Dis. 1992 Jun;51(6):769–776. doi: 10.1136/ard.51.6.769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. FOLEY G. E., LAZARUS H., FARBER S., UZMAN B. G., BOONE B. A., MCCARTHY R. E. CONTINUOUS CULTURE OF HUMAN LYMPHOBLASTS FROM PERIPHERAL BLOOD OF A CHILD WITH ACUTE LEUKEMIA. Cancer. 1965 Apr;18:522–529. doi: 10.1002/1097-0142(196504)18:4<522::aid-cncr2820180418>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  6. Fujino R., Kawato K., Ikeda M., Miyakoshi H., Mizukoshi M., Imai J. Improvement of gelatin particle agglutination test for detection of anti-HTLV-I antibody. Jpn J Cancer Res. 1991 Apr;82(4):367–370. doi: 10.1111/j.1349-7006.1991.tb01856.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Gessain A., Barin F., Vernant J. C., 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. doi: 10.1016/s0140-6736(85)92734-5. [DOI] [PubMed] [Google Scholar]
  9. Green J. E., Hinrichs S. H., Vogel J., Jay G. Exocrinopathy resembling Sjögren's syndrome in HTLV-1 tax transgenic mice. Nature. 1989 Sep 7;341(6237):72–74. doi: 10.1038/341072a0. [DOI] [PubMed] [Google Scholar]
  10. Hinuma Y., Nagata K., Hanaoka M., Nakai M., Matsumoto T., Kinoshita K. I., 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. doi: 10.1073/pnas.78.10.6476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Iwakura Y., Tosu M., Yoshida E., Takiguchi M., Sato K., Kitajima I., Nishioka K., Yamamoto K., Takeda T., Hatanaka M. Induction of inflammatory arthropathy resembling rheumatoid arthritis in mice transgenic for HTLV-I. Science. 1991 Aug 30;253(5023):1026–1028. doi: 10.1126/science.1887217. [DOI] [PubMed] [Google Scholar]
  12. Jacobson S., Shida H., McFarlin D. E., Fauci A. S., Koenig S. Circulating CD8+ cytotoxic T lymphocytes specific for HTLV-I pX in patients with HTLV-I associated neurological disease. Nature. 1990 Nov 15;348(6298):245–248. doi: 10.1038/348245a0. [DOI] [PubMed] [Google Scholar]
  13. Kawase K., Katamine S., Moriuchi R., Miyamoto T., Kubota K., Igarashi H., Doi H., Tsuji Y., Yamabe T., Hino S. Maternal transmission of HTLV-1 other than through breast milk: discrepancy between the polymerase chain reaction positivity of cord blood samples for HTLV-1 and the subsequent seropositivity of individuals. Jpn J Cancer Res. 1992 Sep;83(9):968–977. doi: 10.1111/j.1349-7006.1992.tb02009.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kinoshita T., Shimoyama M., Tobinai K., Ito M., Ito S., Ikeda S., Tajima K., Shimotohno K., Sugimura T. 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. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5620–5624. doi: 10.1073/pnas.86.14.5620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kira J., Koyanagi Y., Yamada T., Itoyama Y., Goto I., Yamamoto N., Sasaki H., Sakaki Y. Increased HTLV-I proviral DNA in HTLV-I-associated myelopathy: a quantitative polymerase chain reaction study. Ann Neurol. 1991 Feb;29(2):194–201. doi: 10.1002/ana.410290214. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Matsumoto C., Mitsunaga S., Oguchi T., Mitomi Y., Shimada T., Ichikawa A., Watanabe J., Nishioka K. Detection of human T-cell leukemia virus type I (HTLV-I) provirus in an infected cell line and in peripheral mononuclear cells of blood donors by the nested double polymerase chain reaction method: comparison with HTLV-I antibody tests. J Virol. 1990 Nov;64(11):5290–5294. doi: 10.1128/jvi.64.11.5290-5294.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Miyakoshi H., Sugimoto M., Igarashi H., Honda H., Fujino R., Mizukoshi M. Improvement of simultaneous detection of antibodies to Gag and envelope antigens of human T-lymphotropic virus type I by western immunoblot assay. J Clin Microbiol. 1992 Oct;30(10):2555–2559. doi: 10.1128/jcm.30.10.2555-2559.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Mochizuki M., Watanabe T., Yamaguchi K., Takatsuki K., Yoshimura K., Shirao M., Nakashima S., Mori S., Araki S., Miyata N. HTLV-I uveitis: a distinct clinical entity caused by HTLV-I. Jpn J Cancer Res. 1992 Mar;83(3):236–239. doi: 10.1111/j.1349-7006.1992.tb00092.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mowbray J., Mawson S., Chawira A., Skidmore S., Boxall E., Desselberger U., Nightingale S. Epidemiology of human T-cell leukaemia/lymphoma virus type 1 (HTLV-1) infections in a subpopulation of Afro-Caribbean origin in England. J Med Virol. 1989 Dec;29(4):289–295. doi: 10.1002/jmv.1890290413. [DOI] [PubMed] [Google Scholar]
  22. Nakajima T., Aono H., Hasunuma T., Yamamoto K., Maruyama I., Nosaka T., Hatanaka M., Nishioka K. Overgrowth of human synovial cells driven by the human T cell leukemia virus type I tax gene. J Clin Invest. 1993 Jul;92(1):186–193. doi: 10.1172/JCI116548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nishioka K., Maruyama I., Sato K., Kitajima I., Nakajima Y., Osame M. Chronic inflammatory arthropathy associated with HTLV-I. Lancet. 1989 Feb 25;1(8635):441–441. doi: 10.1016/s0140-6736(89)90038-x. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. 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. doi: 10.1016/s0140-6736(86)91298-5. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Ponte P., Ng S. Y., Engel J., Gunning P., Kedes L. Evolutionary conservation in the untranslated regions of actin mRNAs: DNA sequence of a human beta-actin cDNA. Nucleic Acids Res. 1984 Feb 10;12(3):1687–1696. doi: 10.1093/nar/12.3.1687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sakai M., Eguchi K., Terada K., Nakashima M., Yamashita I., Ida H., Kawabe Y., Aoyagi T., Takino H., Nakamura T. Infection of human synovial cells by human T cell lymphotropic virus type I. Proliferation and granulocyte/macrophage colony-stimulating factor production by synovial cells. J Clin Invest. 1993 Oct;92(4):1957–1966. doi: 10.1172/JCI116789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sasaki K., Morooka I., Inomata H., Kashio N., Akamine T., Osame M. Retinal vasculitis in human T-lymphotropic virus type I associated myelopathy. Br J Ophthalmol. 1989 Oct;73(10):812–815. doi: 10.1136/bjo.73.10.812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. 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]
  32. 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]
  33. Sugimoto M., Nakashima H., Matsumoto M., Uyama E., Ando M., Araki S. Pulmonary involvement in patients with HTLV-I-associated myelopathy: increased soluble IL-2 receptors in bronchoalveolar lavage fluid. Am Rev Respir Dis. 1989 Jun;139(6):1329–1335. doi: 10.1164/ajrccm/139.6.1329. [DOI] [PubMed] [Google Scholar]
  34. Sugimoto M., Nakashima H., Watanabe S., Uyama E., Tanaka F., Ando M., Araki S., Kawasaki S. T-lymphocyte alveolitis in HTLV-I-associated myelopathy. Lancet. 1987 Nov 21;2(8569):1220–1220. doi: 10.1016/s0140-6736(87)91362-6. [DOI] [PubMed] [Google Scholar]
  35. Vernant J. C., Buisson G., Magdeleine J., De Thore J., Jouannelle A., Neisson-Vernant C., Monplaisir N. T-lymphocyte alveolitis, tropical spastic paresis, and Sjögren syndrome. Lancet. 1988 Jan 23;1(8578):177–177. doi: 10.1016/s0140-6736(88)92744-4. [DOI] [PubMed] [Google Scholar]
  36. Wucherpfennig K. W., Höllsberg P., Richardson J. H., Benjamin D., Hafler D. A. T-cell activation by autologous human T-cell leukemia virus type I-infected T-cell clones. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2110–2114. doi: 10.1073/pnas.89.6.2110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Yoshida M., Osame M., Kawai H., Toita M., Kuwasaki N., Nishida Y., Hiraki Y., Takahashi K., Nomura K., Sonoda S. Increased replication of HTLV-I in HTLV-I-associated myelopathy. Ann Neurol. 1989 Sep;26(3):331–335. doi: 10.1002/ana.410260304. [DOI] [PubMed] [Google Scholar]
  38. 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. doi: 10.1073/pnas.81.8.2534. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES