| Project/Area Number |
18390140
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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 |
Virology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
ADACHI Akio The University of Tokushima, Graduate School Institute of Health Biosciences, Professor (90127043)
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| Co-Investigator(Kenkyū-buntansha) |
UCHIYAMA Tsuneo The University of Tokushima, Graduate School Institute of Health Biosciences, Associate professor (90151901)
YAMASHITA Tomoki The University of Tokushima, Graduate School Institute of Health Biosciences, Assistant Professor (70380087)
NOMAGUCHI Masako The University of Tokushima, Graduate School Institute of Health Biosciences, Assistant Professor (80452647)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,720,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2007: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2006: ¥8,400,000 (Direct Cost: ¥8,400,000)
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| Keywords | HIV-1 / SIVmac / Gag-CA / Vif / CVp3 A / TRIM5 a / APOBEC / Monkey-tropism / サル指向性 / X4ウイルス / R5ウイルス / 馴化 / MNクローン / ウイルス / 種特異性 / シクロフィリンA結合領域 |
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| Research Abstract |
HIV-I possesses a tightly restricted species tropism, and is pathogenic only for humans. It has been, therefore, impossible to perform the animal experiments critical for studies on highly pathogenic viruses such as HIV-1. We recently have successfully constructed a monkey-tropic HIV-I for the first time in the world. This virus has the SIV homologues of HIV-1 CypA-binding region in Gag-CA and Vif. In this research project, we aimed at : 1. determination of genomic regions responsible for monkey cell tropism, 2. elucidation of the mechanism for monkey cell tropism, 3. generation and characterization of virus clones that are adapted to grow well in monkey cells, 4. generation of monkey cell-tropic R5 viruses, 5. generation and characterization of mutants of accessory genes. A prototype monkey-tropic HIV-1 (X4) was found to infect pig-tailed and cynomolgus monkeys and to induce immunological reactions. However, it grew more poorly than the pathogenic standard SIVmac in monkey cells and in animals. A growth-defect of this virus concerning TRIM5α-restriction was successfully repaired considerably by altering a region in Gag-CA to improve its growth ability in monkey cells. We also have obtained cell-adapted virus clones (X4 and R5) with replication potentials similar to that of SIVmac. We finally generated proviral molecular clones which carry all the mutations described above, and mutants of accessory genes derived from them. We are now ready to perform animal experiments for various HIV-1/AIDS studies on basic (underlying mechanisms for viral replication and pathogenicity ; in vivo roles of accessory proteins) and clinical issues.
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