Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1991 Oct;88(4):1315–1322. doi: 10.1172/JCI115436

Detection of human T cell lymphotropic virus type I proviral DNA and its gene expression in synovial cells in chronic inflammatory arthropathy.

I Kitajima 1, K Yamamoto 1, K Sato 1, Y Nakajima 1, T Nakajima 1, I Maruyama 1, M Osame 1, K Nishioka 1
PMCID: PMC295601  PMID: 1680881

Abstract

To investigate the pathogenesis of human T cell lymphotropic virus type I (HTLV-I)-associated chronic inflammatory arthropathy (HAAP), we sought to detect proviral DNA in the articular lesions. For the detection of proviral DNA, we used the polymerase chain reaction (PCR). Proviral DNA was detected not only in the peripheral blood mononuclear cells (PBMCs) and synovial fluid cells (SFCs), but also in the T lymphocyte-depleted cultured synovial cells (CSCs). These findings suggest that the infection by HTLV-I might occur in vivo in non-T cells. Furthermore, we detected HTLV-I tax1/rex1 messenger RNA in fresh synovial tissues and CSCs but not in fresh PBMCs and fresh SFCs using reverse transcription and PCR. Immunohistochemically, the CSCs from HAAP patients were also shown to express the HTLV-I antigens. These data indicate that HTLV-I in the non-T synovial cells can be transcribed and expressed. Moreover, the sequences of pXII regions in the CSCs demonstrated 97.5-99.4% homology to that in MT-2 cells, HTLV-I-infected cell line. This confirmed that the PCR-amplified bands reflect HTLV-I itself. These results suggest that this organ-specific inflammation can be attributed to non-T cell virus infection in articular lesions.

Full text

PDF
1315

Images in this article

Selected References

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

  1. 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]
  2. Bentin J., Feremans W., Pasteels J. L., Hauzeur J. P., Menu R., Appelboom T. Chronic acquired immunodeficiency syndrome-associated arthritis: a synovial ultrastructural study. Arthritis Rheum. 1990 Feb;33(2):268–273. doi: 10.1002/art.1780330217. [DOI] [PubMed] [Google Scholar]
  3. Blin N., Stafford D. W. A general method for isolation of high molecular weight DNA from eukaryotes. Nucleic Acids Res. 1976 Sep;3(9):2303–2308. doi: 10.1093/nar/3.9.2303. [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. 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]
  7. Greenberg S. J., Ehrlich G. D., Abbott M. A., Hurwitz B. J., Waldmann T. A., Poiesz B. J. 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. doi: 10.1073/pnas.86.8.2878. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hiramatsu K., Nishida J., Naito A., Yoshikura H. Molecular cloning of the closed circular provirus of human T cell leukaemia virus type I: a new open reading frame in the gag-pol region. J Gen Virol. 1987 Jan;68(Pt 1):213–218. doi: 10.1099/0022-1317-68-1-213. [DOI] [PubMed] [Google Scholar]
  9. Hospice comes of age. Lancet. 1986 May 3;1(8488):1013–1014. [PubMed] [Google Scholar]
  10. Hoxie J. A., Matthews D. M., Cines D. B. Infection of human endothelial cells by human T-cell leukemia virus type I. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7591–7595. doi: 10.1073/pnas.81.23.7591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Kennedy-Stoskopf S., Zink M. C., Jolly P. E., Narayan O. Lentivirus-induced arthritis. Chronic disease caused by a covert pathogen. Rheum Dis Clin North Am. 1987 Aug;13(2):235–247. [PubMed] [Google Scholar]
  13. 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]
  14. Kitajima I., Maruyama I., Maruyama Y., Ijichi S., Eiraku N., Mimura Y., Osame M. Polyarthritis in human T lymphotropic virus type I-associated myelopathy. Arthritis Rheum. 1989 Oct;32(10):1342–1344. doi: 10.1002/anr.1780321030. [DOI] [PubMed] [Google Scholar]
  15. Kwok S., Ehrlich G., Poiesz B., Kalish R., Sninsky J. J. Enzymatic amplification of HTLV-I viral sequences from peripheral blood mononuclear cells and infected tissues. Blood. 1988 Oct;72(4):1117–1123. [PubMed] [Google Scholar]
  16. Liberski P. P., Rodgers-Johnson P., Char G., Piccardo P., Gibbs C. J., Jr, Gajdusek D. C. HTLV-I-like viral particles in spinal cord cells in Jamaican tropical spastic paraparesis. Ann Neurol. 1988;23 (Suppl):S185–S187. doi: 10.1002/ana.410230741. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. 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]
  20. 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]
  21. Reddy E. P., Sandberg-Wollheim M., Mettus R. V., Ray P. E., DeFreitas E., Koprowski H. Amplification and molecular cloning of HTLV-I sequences from DNA of multiple sclerosis patients. Science. 1989 Jan 27;243(4890):529–533. doi: 10.1126/science.2536193. [DOI] [PubMed] [Google Scholar]
  22. Rowe I. F., Keat A. C. Human immunodeficiency virus infection and the rheumatologist. Ann Rheum Dis. 1989 Feb;48(2):89–91. doi: 10.1136/ard.48.2.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. Saito I., Servenius B., Compton T., Fox R. I. Detection of Epstein-Barr virus DNA by polymerase chain reaction in blood and tissue biopsies from patients with Sjogren's syndrome. J Exp Med. 1989 Jun 1;169(6):2191–2198. doi: 10.1084/jem.169.6.2191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Salahuddin S. Z., Markham P. D., Lindner S. G., Gootenberg J., Popovic M., Hemmi H., Sarin P. S., Gallo R. C. Lymphokine production by cultured human T cells transformed by human T-cell leukemia-lymphoma virus-I. Science. 1984 Feb 17;223(4637):703–707. doi: 10.1126/science.6320367. [DOI] [PubMed] [Google Scholar]
  27. Salahuddin S. Z., Markham P. D., Wong-Staal F., Franchini G., Kalyanaraman V. S., Gallo R. C. Restricted expression of human T-cell leukemia--lymphoma virus (HTLV) in transformed human umbilical cord blood lymphocytes. Virology. 1983 Aug;129(1):51–64. doi: 10.1016/0042-6822(83)90395-1. [DOI] [PubMed] [Google Scholar]
  28. Scharf S. J., Long C. M., Erlich H. A. Sequence analysis of the HLA-DR beta and HLA-DQ beta loci from three Pemphigus vulgaris patients. Hum Immunol. 1988 May;22(1):61–69. doi: 10.1016/0198-8859(88)90052-3. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. 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]
  31. Shimotohno K., Takahashi Y., Shimizu N., Gojobori T., Golde D. W., Chen I. S., Miwa M., Sugimura T. Complete nucleotide sequence of an infectious clone of human T-cell leukemia virus type II: an open reading frame for the protease gene. Proc Natl Acad Sci U S A. 1985 May;82(10):3101–3105. doi: 10.1073/pnas.82.10.3101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Smith L. M., Sanders J. Z., Kaiser R. J., Hughes P., Dodd C., Connell C. R., Heiner C., Kent S. B., Hood L. E. Fluorescence detection in automated DNA sequence analysis. Nature. 1986 Jun 12;321(6071):674–679. doi: 10.1038/321674a0. [DOI] [PubMed] [Google Scholar]
  33. Sokoloff L. A prospective necropsy study of arthritis in acquired immunodeficiency syndrome. Arch Pathol Lab Med. 1990 Oct;114(10):1035–1037. [PubMed] [Google Scholar]
  34. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Taniguchi A., Takenaka Y., Noda Y., Ueno Y., Shichikawa K., Sato K., Miyasaka N., Nishioka K. Adult T cell leukemia presenting with proliferative synovitis. Arthritis Rheum. 1988 Aug;31(8):1076–1077. doi: 10.1002/art.1780310824. [DOI] [PubMed] [Google Scholar]
  37. Tomita S., Ambrus J. L., Jr, Volkman D. J., Longo D. L., Mitsuya H., Reitz M. S., Jr, Fauci A. S. Human T cell leukemia/lymphoma virus I infection and subsequent cloning of normal human B cells. Direct responsiveness of cloned cells to recombinant interleukin 2 by differentiation in the absence of enhanced proliferation. J Exp Med. 1985 Jul 1;162(1):393–398. doi: 10.1084/jem.162.1.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. 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]
  39. 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]
  40. Wano Y., Hattori T., Matsuoka M., Takatsuki K., Chua A. O., Gubler U., Greene W. C. Interleukin 1 gene expression in adult T cell leukemia. J Clin Invest. 1987 Sep;80(3):911–916. doi: 10.1172/JCI113152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Watanabe T., Seiki M., Tsujimoto H., Miyoshi I., Hayami M., Yoshida M. Sequence homology of the simian retrovirus genome with human T-cell leukemia virus type I. Virology. 1985 Jul 15;144(1):59–65. doi: 10.1016/0042-6822(85)90304-6. [DOI] [PubMed] [Google Scholar]
  42. Wiley C. A., Nerenberg M., Cros D., Soto-Aguilar M. C. HTLV-I polymyositis in a patient also infected with the human immunodeficiency virus. N Engl J Med. 1989 Apr 13;320(15):992–995. doi: 10.1056/NEJM198904133201507. [DOI] [PubMed] [Google Scholar]
  43. 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]
  44. Yoshida M., Osame M., Usuku K., Matsumoto M., Igata A. Viruses detected in HTLV-I-associated myelopathy and adult T-cell leukaemia are identical on DNA blotting. Lancet. 1987 May 9;1(8541):1085–1086. doi: 10.1016/s0140-6736(87)90506-x. [DOI] [PubMed] [Google Scholar]
  45. 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]
  46. Yoshikura H., Nishida J., Yoshida M., Kitamura Y., Takaku F., Ikeda S. Isolation of HTLV derived from Japanese adult T-cell leukemia patients in human diploid fibroblast strain IMR90 and the biological characters of the infected cells. Int J Cancer. 1984 Jun 15;33(6):745–749. doi: 10.1002/ijc.2910330606. [DOI] [PubMed] [Google Scholar]
  47. Ziegler B., Gay R. E., Huang G. Q., Fassbender H. G., Gay S. Immunohistochemical localization of HTLV-I p19- and p24-related antigens in synovial joints of patients with rheumatoid arthritis. Am J Pathol. 1989 Jul;135(1):1–5. [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES