| Project/Area Number |
18390141
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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 | Kumamoto University |
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Principal Investigator |
TAKIGUCHI Masafumi Kumamoto University, Center for AIDS Research, Professor (00183450)
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| Co-Investigator(Kenkyū-buntansha) |
OKA Shinichi Kumamoto University, International Medical Center of Japan, ACC Director (20194326)
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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 |
¥16,310,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2007: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2006: ¥7,600,000 (Direct Cost: ¥7,600,000)
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| Keywords | Virus / Pathogenesis / Control of infection / HIV-1 / T Cell |
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| Research Abstract |
It is well known that HLA-B^*57/58, -B^*27, and -B*^51 alleles are associated with slow disease progression to AIDS, but the role of cytotoxic T lymphocytes(CTLs)restricted by these alleles in long-term control of HIV-1 still remains unknown. We investigated HIV-1-specific CTLs in long-term non-progressing(LTNP)and slow-progressing(slow progressors)hemophiliacs carrying HLA-B^*5101. Both Pol283-8-specific and Pol743-9-specific CTLs, which have a strong ability to suppress HIV-1 replication in vitro, were detected in LTNPs whereas only Pol743-9-specific CTLs were found in the slow progressors. The LTNPs had HIV-1 possessing wild-type sequence in these epitopes or a mutation reducing the ability of the specific CTLs to suppress HIV-1 replication and viral fitness. In contrast, the slow progressors and progressors had HIV-1 with escape mutations that did not influence viral fitness. Longitudinal analysis of a hemophiliac confirmed the association between the appearance of a Pol283-8 escape mutant and a high viral load. The induction of HIV-1-specific CTLs with a strong ability to suppress HIV-1 replication and the evolution to a mutant with reduced viral fitness and T cell recognition were found to be necessary for the control of HIV-1 for approximately 25 years.
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