| Project/Area Number |
10670279
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Kumamoto University (1999)
University of Tsukuba (1998) |
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Principal Investigator |
KOITO Atsushi AIDS Research Center, Kumamoto University, Asso. Professor, エイズ学研究センター, 講師 (70231305)
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| Co-Investigator(Kenkyū-buntansha) |
小糸 厚 熊本大学, エイズ学研究センター, 講師 (70231305)
中内 啓光 筑波大学, 基礎医学系, 教授 (40175485)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | HTLV-1 / Receptor / Mouse lymphocytes / Integration / Transgenic mouse / HTLV-l / HTLV-I 感染 / エンベロープ / レセプター / マウスモデル |
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| Research Abstract |
We have generated transgenic mice predominantly expresing T-tropic HIV-1 receptors, human CD4 and CXCR4 on their CD4-positive T lymphocytes. Our data suggest that the dual function of CXCR4 in HIV-1 infection and in lymphocyte trafficking may cooperatvely induce progressive HIV-1 infection and CD4-positive T cell decline in patients.
For understanding the pathogenesis of retroviral infection, it is necessary to identify the receptor molecule(s) which determine the host, tissue specificity of retrovirus replication. However, HIV-1 replication in these CD4 and CXCR4 double transgenic mice are found to be severely impared, limiting the use of mice in the studies for understanding the mechanism of HIV-1 pathogenesis in vivo. Preintegration forms of provirus are observed following infection of these mouse lymphoid cells, however the efficiency of integration into the chromosome of these cells were found to be much lower than that of human cell (Koito.A., Nagasawa.T., Suzuki.G., Matsushita.S., manuscript in preparation).
Further studies are required to characterize the barrier exist mouse cells, and approaches to overcome the resistance of mouse lymphoid cells to human retrovirus infection may permit developing a rodent model that would present many obvious advantages. For identification of HTLV-1 receptor(s), we have generated cDNA libraries from activated human PBMC and packaged them into the retrovirus vector. Expression cloning of the molecules which involve in HYLV-1 infection is in progress.
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