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EXPRESSION OF HUMAN ENDOGENOUS RETROVIRUS AND ITS POSSIBLE ROLES FOR DEVELOPING AUTOIMMUNE DESIASES

Research Project

Project/Area Number 15590330
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

TOMARU Utano (2004)  Hokkaido Univ., Grad.School of Med., Lecturer, 大学院・医学研究科, 講師 (20360901)

池田 仁 (2003)  北海道大学, 大学院・医学研究科, 助教授 (20232192)

Co-Investigator(Kenkyū-buntansha) ISHIZU Akihiro  Hokkaido Univ., Grad.School of Med., Lecturer, 大学院・医学研究科, 講師 (60321957)
SUZUKI Akira  Hokkaido Univ., Grad.School of Med., Instructor, 大学院・医学研究科, 助手 (50374236)
外丸 詩野  北海道大学, 大学院・医学研究科, 助手 (20360901)
吉木 敬  北海道大学, 大学院・医学研究科, 教授 (60220612)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordshuman endogenous retrovirus / transgenic rat / tissue-specific expression / targeted antigen / autoimmune disease / トランシジェニックラット / タンパク発現 / 蛋白発現 / 発生と分化
Research Abstract

The aims of this project were to investigate the biological role of human endogenous retrovinis-R (HERV-R) in vivo. We have established transgenic rats carrying a full sequence of HERV-R under control of its own long terminal repeat promoter (HERV-R rat), and analyzed HERV-R expression and its possible roles for developing autoirnmune disease. Major research accomplishments were as follows :
1.The product of the transgene was detected as an 85 kDa glycoprotein in specific organs such as Harderian gland, prostatic gland, skin and salivary gland.
2.We have found that skin tissues transplanted from HERV-R rats to wild rats are rejected around 50 days after transplantation, suggesting that HERV-R antigen is recognized as a target antigen in the immune responses.
3.Because we observed no pathological significance in the HERV-R rats, we have established double transgenic rats carrying both human infectious retrovirus HTLV-I env-pX gene and HERV-R gene. Based on our previous studies, transgenic rat carrying HTLV-I env-pX gene indicate significant pathological findings which are similar to human autoimmune disorders. We have postulated that HERV-R antigen may modulate immune responses in the rats with a background of auto-immune responses. We observed that double transgenic rats had a tendency to be short-lived, and we found deposition of IgM-type autoantibodies in the Harderian gland. We also found thrombus formation in the glomeruli of kidney by histopathological analysis.
4.Based on our experiments, we propose a possibility that expression of endogenous retrovirus may modulate immune responses in the inflammatory diseases including autoimmune disorders.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (38 results)

All 2005 2004 2003 Other

All Journal Article (30 results) Publications (8 results)

  • [Journal Article] Aberrant gene expression by CD25+CD4+ immunoregulatory T cells in auto immune-prine rats carrying the human T cell leukemia virus type-I gene.2005

    • Author(s)
      Hayase, H., et al.
    • Journal Title

      International Immunology (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Aberrant gene expression by CD25+CD4+ immunoregulatory T cells in autoimmune-prone rats carrying the human T cell leukemia virus type-I gene.2005

    • Author(s)
      Hayasa H, Ishizu A, Ikeda H, Miyatake Y, Baba T, Higuchi M, Abe A, Tomaru U, Yoshiki T.
    • Journal Title

      Int Immunol (in press)

    • NAID

      10019358360

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Aberrant gene expression by CD25+CD4+ immunoregulatory T cells in autoimmune-prone rats carrying the human T cell leukemia virus type-I gene.2005

    • Author(s)
      Hayase, H., et al.
    • Journal Title

      International Immunology (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Hematopoietic progenitor cells as possible origins of epithelial thymoma in a human T lymphocyte virus type I pX gene transgenic rat model.2004

    • Author(s)
      Tsuchikawa, T., et al.
    • Journal Title

      Laboratory Investigation 84・2

      Pages: 245-252

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Bone marrow cells carrying env-pX transgene play a role in the severity but not prolongation of arthritis in human T-cell leukemia virus type-I transgenic rats : a possible role of articular tissues carrying the transgene in the prolongation of arthritis.2004

    • Author(s)
      Abe, A., et al.
    • Journal Title

      International Journal of Experimental Pathology 85

      Pages: 191-200

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Differential modulation of gene expression among rat tissues with warm ischemia.2004

    • Author(s)
      Miyatake, Y., et al.
    • Journal Title

      Experimental Molecular Pathology 77

      Pages: 222-230

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Dexamethasone increased plasminogen activator inhibitor-1 expression on human umbilical vein endothelial cells : an additive effect to tumor necrosis factor-alpha.2004

    • Author(s)
      Yamanoto, Y., et al.
    • Journal Title

      Pathobiology 71

      Pages: 295-301

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Increased expression of HTLV-I Tax11-19 peptide/HLA-A^*201 complexes on CD4+CD25+ T cells detected by peptide-specific, MHC restricted antibodies in patients with HTLV-I associated neurologic disease.2004

    • Author(s)
      Yamano, Y., et al.
    • Journal Title

      Journal of Experimental Medicine 199

      Pages: 1367-1377

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hematopoietic progenitor cells as possible origins of epithelial thymoma in a human T lymphocyte virus type I pX gene transgenic rat model.2004

    • Author(s)
      Tsuchikawa, T., Ikeda, H., Kikuchi, K., Tsuji, T., Baba, T., Ishizu, A., Tanaka, Y., Kate, H, Yoshiki, T.
    • Journal Title

      Lab Invest 84

      Pages: 245-252

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Bone marrow cells carrying the env-pX transgene play a role in the severity but not prolongation of arthritis in human T-cell leukaemia virus type-I transgenic rats : a possible role of articular tissues carrying the transgene in the prolongation of arthritis.2004

    • Author(s)
      Abe, A., Ishizu, A., Ikeda, H., Hayase, H., Tsuji, T., Miyatake, Y., Tsuji, M., Fugo, K., Sugaya, T., Higuchi, M., Matsuno, T., Yoshiki, T.
    • Journal Title

      Int J Exp Pathol 85(4)

      Pages: 191-200

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Differential modulation of gene expression among rat tissues with warm ischemia.2004

    • Author(s)
      Miyatake, Y., Ikeda, H., Michimata, R., Koizumi, S., Ishizu, A., Nishimura, N., Yoshiki, T.
    • Journal Title

      Exp Mol Pathol 77(3)

      Pages: 222-230

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dexamethasone increased plasminogen activator inhibitor-1 expression on human umbilical vein endothelial cells : an additive effect to tumor necrosis factor-alpha.2004

    • Author(s)
      Yamamoto, Y., Ishizu, A., Ikeda, H., Otsuka, N., Yoshiki, T.
    • Journal Title

      Pathobiology 71(6)

      Pages: 295-301

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Increased expression of human T lymphocyte virus type I (HTLV-I) Tax11-19 peptide-human histocompatibility leukocyte antigen A^*201 complexes on CD4+ CD25+ T Cells detected by peptide-specific, major histocompatibility complex-restricted antibodies in patients with HTLV-I-associated neurologic disease.2004

    • Author(s)
      Yamano, Y., Cohen, C.J., Takenouchi, N., Yao, K., Tomaru, U., Li, H.C., Reiter, Y., Jacobson, S.
    • Journal Title

      J Exp Med 199(10)

      Pages: 1367-1377

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Bone marrow cells carrying the env-pX transgene play a role in the severity but notprolongation of arthritis in human T-cell leukaemia virus type-I transgenic rats : a possible role of articular tissues carrying the transgene in the prolongation of arthritis.2004

    • Author(s)
      Abe, A., et al.
    • Journal Title

      International Journal of Experimental Pathology 85

      Pages: 191-200

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Dexamethasone increased plasminogen activator inhibitor-1 expression on human umbilical vein endothelial cells : an additive effect to tumor necrosis factor-alpha.2004

    • Author(s)
      Yamamoto, Y., et al.
    • Journal Title

      Pathobiology 71

      Pages: 295-301

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Increased expression of HTLV-I Tax11-19 peptide/HLA-A^*201 complexes on CD4+ CD25+ T cells detected by peptide-specific, MHC restricted antibodies in patients with HTLV-I associated neurologic disease.2004

    • Author(s)
      Yamono, Y. et al.
    • Journal Title

      Journal of Experimental Medicine 199

      Pages: 1367-1377

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Transduction of dominant negative ATF-1 suppresses the pX gene expression in joint fibroblastic cells derived from HTLV-I transgenic rats.2003

    • Author(s)
      Ishizu, A., et al.
    • Journal Title

      Experimental Molecular Pathology 74

      Pages: 309-313

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Functional alteration of peripheral CD25+CD4+immunoregulatory T cells in a transgenic rat model of autoimmune diseases.2003

    • Author(s)
      Higuchi, M., et al.
    • Journal Title

      Journal of Autoimmunity 20

      Pages: 43-49

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Tissue specific high level expression of a full human endogenous retrovirus genome transgene, HERV-R, under control of its own promoter in rats.2003

    • Author(s)
      Tanaka, T., et al.
    • Journal Title

      Transgenic Research 12

      Pages: 319-328

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Epstein-Barr virus infection of rat lymphocytes expressing human CD21 results in restricted latent virus gene expression but not in immunoblastic transformation.2003

    • Author(s)
      Yang, L., et al.
    • Journal Title

      Journal of Medical Virology 70

      Pages: 126-130

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Vaccination of fusion cells of rat dendritic and carcinoma cells prevents tumor growth in vivo.2003

    • Author(s)
      Kawada, M., et al.
    • Journal Title

      International Journal of Cancer 105

      Pages: 520-526

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Provirus expansion and deregulation of apoptosis-regulated genes in the spinal cord of a rat model for human T lymphocyte virus type I-associated myeloneuropathy.2003

    • Author(s)
      Tomaru, U., et al.
    • Journal Title

      Journal of Neurovirology 9

      Pages: 530-538

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] In vitro model of suicide gene therapy for alpha-fetoprotein-producing gastric cancer.2003

    • Author(s)
      Nakaya, H., et al.
    • Journal Title

      Anticancer Research 23

      Pages: 3795-3800

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Transduction of dominant negative ATF-1 suppresses the pX gene expression in joint fibroblastic cells derived from HTLV-I transgenic rats.2003

    • Author(s)
      Ishizu, A., Tsuji, T., Abe, A., Saito, S., Takahashi, T., Ikeda, H., Meruelo, D., Yoshiki, T.
    • Journal Title

      Exp Mol Pathol 74

      Pages: 309-313

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Functional alteration of peripheral CD25^+CD4^+ immunoregulatory T cells in a transgenic rat model of autoimmune diseases.2003

    • Author(s)
      Higuchi, M., Ishizu, A., Ikeda, H., Hayase, H., Fugo, K., Tsuji, M., Abe, A., Sugaya, T., Suzuki, A., Takahashi, T., Koike, T., Yoshiki, T.
    • Journal Title

      J Autoimmunity 20

      Pages: 43-49

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Tissue specific high level expression of a full length human endogenous retrovirus genome transgene, HERV-R, under control of its own promoter in rats.2003

    • Author(s)
      Tanaka, S., Ikeda, H., Otsuka, N., Yamamoto, Y., Sugaya, T., Yoshiki, T.
    • Journal Title

      Transgenic Research 12

      Pages: 319-328

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Epstein-Barr virus infection of rat lymphocytes expressing human CD21 results in restricted latent viral gene expression and not in immunoblastic transformation.2003

    • Author(s)
      Yang, L., Ikeda, H., Lat, Y., Yoshiki, T., Takada, K.
    • Journal Title

      J Med viral 70

      Pages: 126-130

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Vaccination of fusion cells of rat dendritic and carcinoma cells prevents tumor growth in vivo.2003

    • Author(s)
      Kawada, M., Ikeda, H., Takahashi, T., Ishizu, A., Ishikura, H., Katoh, H., Yoshiki, T.
    • Journal Title

      Int J Cancer 105

      Pages: 520-526

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Provirus expansion and deregulation of apoptosis-related genes in the spinal cord of a rat model for human T-lymphocyte virus type I-associated myeloneuropathy.2003

    • Author(s)
      Tomaru, U., Ikeda, H., Jiang, X., Ohya, O., Yoshiki, T.
    • Journal Title

      J Neurovirol 9

      Pages: 530-538

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] In vitro model of suicide gene therapy for alpha-fetoproteinproducing gastric cancer.2003

    • Author(s)
      Nakaya, H., Ishizu, A., Ikeda, H., Tahara, M., Shindo, J., Itoh, R., Takahashi, T., Asaka, M., Hiroshi, I., Yoshiki, T.
    • Journal Title

      Anticancer Res. 23

      Pages: 3795-3800

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Ishizu, A., et al.: "Transduction of dominal negative ATF-1 suppresses the pX gene expression in joint fibroblastic cells derived from HTLV-1 transgenic rats"Experimental Molecular Pathology. 74. 309-313 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Higuchi, M., et al.: "Functional alteration of peripheral CD25+CD4+immunoregulatory T cells in a transgenic rat model of autoimmune diseases"Journal of Autoimmunity. 20. 43-49 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tanaka, T., et al.: "Tissue spec high level expression of a full human endogenous retrovirus genome transgene, HERV-R, under control of its own promoter in rats"Transgenic Research. 12. 319-328 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yang, L., et al.: "Epstein-Barr virus infection of rat lymphocytes expressing human CD21 results in restricted latent virus gene expression but not in immunoblastic transformation"Journal of Medical Virology. 70. 126-130 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kawada, M., et al.: "Vaccination of fusion cells of rat dendritic and carcinoma cells prevents tumor growth in vivo"International Journal of Cancer. 105. 520-526 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tomaru, U., et al.: "Provirus expansion and deregulation of apoptosis-regulated genes in the spinal cord of a rat model for human T lymphocyte virus type I-associated myeloneuropathy"Journal of Neurovirology. 9. 530-538 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakaya, H., et al.: "In vitro model of suicide gene therapy for alpha-fetoprotein-producing gastric cancer"Anticancer Research. 23. 3795-3800 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsuchikawa, T. et al.: "Hematopoletic progenitor cells as possible origins of epithelial thymoma in a human T lymphocyte virus type I pX gene transgenic rat model"Laboratory Investigation. 84・2. 245-252 (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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