Development of novel therapeutic strategies for AIDS by the molecular regulation strategies for feline immunodeficiency virus infection
| Project/Area Number |
15380209
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied veterinary science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TSUJIMOTO Hajime The University of Tokyo, Graduate School of Agricultural and life Sciences, Professor (60163804)
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| Co-Investigator(Kenkyū-buntansha) |
OHNO Koichi The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate professor (90294660)
IWATA Akira Nippon Institute of Biological Science, 研究部, Project leader (70193745)
増田 健一 東京大学, 大学院・農学生命科学研究科, 助手 (40313077)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 2004: ¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 2003: ¥7,000,000 (Direct Cost: ¥7,000,000)
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| Keywords | cat / feline immunodeficiency virus / antiviral therapy / RNA interference / chemokine receptor / fusion inhibitor / dendritic cell / animal model / 猫免疫不全ウイルス / 遺伝子治療 / 免疫療法 / small interfering RNA / 骨髄内投与 / レトロウイルスベクター / ネコ / 感染症 / 治療 |
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| Research Abstract |
A series of studies were performed in order to develop novel therapeutic strategies specific to feline immunodeficiency virus (FIV) infection.
1. A therapeutic strategy using RNA interference was employed to inhibit the gene expression of FIV. Transfection of plasmid vectors expressing FIV-specific shRNA into FIV-infected feline cell lines resulted in the consistent suppression of the expression of FIV mRNA/protein and reverse transcriptase.
2. Antiviral effect of several types of CXC-chemokine receptor inhibitors (CXCR4 antagonists) was investigated. C-terminal amidated CXCR4 antagonists synthesized to increase the biostability showed a significant activity to inhibit the replication of FIV.
3. Antiviral effect of the fusion-associated heptad repeat and its derivatives of FIV gp40 was examined. The study revealed several fusion peptides that showed strong antiviral effect for various FIV strains of different subtypes.
4. To develop immunotherapy using dendritic cells (DC), feline peripheral blood monocytes were cultured in the presence of various cytokines. These cells were shown to have dendritic projections and immunological phenotypes characteristic to DC. Function of DC was maintained in asymptomatic carrier cats infected with FIV.
The present study provided innovative findings to develop antiviral therapies in FIV infection. With respect to the RNA interference, viral receptor, membrane fusion, and DC, there is a remarkable similarity between FIV infection in cats and AIDS in humans ; thus, the results obtained in this study can be also useful to utilize the feline system as an animal model of AIDS in humans.
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Report
(3 results)
Research Products
(56 results)
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[Publications] Mizuno, T., Goto, Y., Baba, K., Masuda, K., Ohno, K., Tsujimoto, H.: "Molecular cloning of feline tumor necrosis factor receptor type I (TNFR I) and expression of TNFR I and TNFR II in lymphoid cells in cats."Eur.J.Immunogenetics. 30. 107-113 (2003)
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[Publications] Mizuno, T., Goto, Y., Baba, K., Momoi, Y., Endo, Y., Nishimura, K., Masuda, K., Ohno, K., Tsujimoto, H.: "Quantification analysis of Fas and Fas ligand mRNAs in feline T lymphoid cell lines after infection with feline immunodeficiency virus and primary peripheral blood mononuclear cells obtained from cats infected with the virus."Vet.Immunol.Imunopathol.. 93. 117-123 (2003)
