| Project/Area Number |
14207010
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KYOSHIKI Takashi Hokkaido Univ., Grad.School of Med., Prof., 大学院・医学研究科, 教授 (60220612)
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| Co-Investigator(Kenkyū-buntansha) |
TOMARU Utano Hokkaido Univ., Grad.School of Med., Inst., 大学院・医学研究科, 助手 (20360901)
ISHIZU Akihiro Hokkaido Univ., Grad.School of Med., Lec., 大学院・医学研究科, 講師 (60321957)
IKEDA Hitoshi Hokkaido Univ., Grad.School of Med., Asso.Prof., 大学院・医学研究科, 助教授 (20232192)
高橋 利幸 北海道大学, 大学院・医学研究科, 講師 (40261284)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥43,290,000 (Direct Cost: ¥33,300,000、Indirect Cost: ¥9,990,000)
Fiscal Year 2003: ¥20,150,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥4,650,000)
Fiscal Year 2002: ¥23,140,000 (Direct Cost: ¥17,800,000、Indirect Cost: ¥5,340,000)
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| Keywords | retrovirus / HTLV-I / HIV-1 / animal model / myelopathy / transgenic / autoimmune disease / thymoma / HIV-I / 免疫制御細胞 / レトロウィルス / Cyclin T1 |
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| Research Abstract |
Virus-host interactions were investigated using rat models for human retrovirus-induced diseases.
1.HAM rat disease occurred in HTLV-I-infected rats in a strain-dependent manner. In HAM susceptible rats, expression of the INF-γ gene in the spinal cord did not increase after HTLV-I infection, while did in HAM resistant strains. These findings suggest that INF-γ may play a role in prevention at HTLV-1-induced diseases.
2.Autoimmune diseases occurred in HTLV-I LTR-env-pX transgenic rats (LTR-env-pX rats). Functional alteration of CD25+CD4+ immunoregulatory T-cells was evident in LTR-env-pX rats before they developed diseases. Expressions of the CTLA-4, GITR, Foxp3, and SOCS family genes in the cells of LTR-env-pX rats were lower than those of wild type rats. Synovial tissues rather than bone marrow cells carrying the transgene may play roles in prolongation of arthritis developed in LTR-env-pX rats.
3.Benign epithelial thymoma occurred in lck-pX transgenic rats (lck-pX rats). Thymoma grafted in the subcapsular space of the kidney of lck-pX rats showed malignant transformation. The p16/ARF genes were lost in the transformed tumors, thus suggesting that these molecules may be associated with malignant transformation of HTLV-I-induced neoplasms.
4.Rat fibrobalastic cells expressing human CD4 and CXCR-4/CCR5 could be infected with HIV-1. Although HIV-1 provirus was integrated in the genome of these cells, viral expression was not achieved completely. Putative factors including human cyclin T1 and MHC class II transactivator (C2TA) may be needed for viral replication in the cells. To examine interactions of HIV-1 and host in vivo, transgenic rats carrying the human CD4, CXCR4/CCR5, cyclic T1, and C2TA genes were established.
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