| Project/Area Number |
10470078
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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 Univ. Tokushima Sch. Med, Professor, 医学部, 教授 (90127043)
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| Co-Investigator(Kenkyū-buntansha) |
AKARI Hirofumi Univ. Tokushima Sch. Med, Assistant Professor, 医学部, 助手 (20294671)
KOYAMA Hajime Univ. Tokushima Sch. Med, Associate Professor, 医学部, 助教授 (80109074)
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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 |
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 1999: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 1998: ¥8,700,000 (Direct Cost: ¥8,700,000)
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| Keywords | HIV / Nef / Vpr / MHC-I / CD4 / Apoptosis |
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| Research Abstract |
In this study, we have demonstrated the detaild action mechanisms of HIV-1 Nef and the strong apoptosis-inducing ability of HIV-1 Vpr.
HIV-1 Nef has been reported to act via modulation of viral particles to enhance virus infectivity. We showed that HIV-1 virions produced in the absence of Nef are defective for the processes of virus entry and DNA synthesis. Requirement of HIV-1 Nef for efficient entry of HIV-l into cells was producer cell-dependent The PxxP and RR domains were both dispensable for enhanced viral entry, thus suggesting that another interaction of Nef with a cellular factor(s) is involved in the process of viral entry. It has been reported that various important functions such as the viral infectivity, incorporation of Nef into virions, and down-regulation of MHC-I are mapped to the N-terminal portion of HIV-1 Nef. We showed, by the analysis of point mutants regarding 20th amino acid of the Nef, that Nef-induced MHC-I down-regulation is functionally dissociated from its virion incorporation, enhancement of viral infectivity, and CD4 down-regulation.
It is controversial about the regulation of apoptosis by Vpr. Some report that Vpr induces apoptosis, and others that Vpr shows anti-apoptotic function. To determine whether HIV-1 Vpr is an inducer of apoptosis, we analyzed the cells infected with HIV-1/VSV pseudotype virus. This system does not require the selection of cells producing Vpr, and thus it is possible to directly monitor the apoptosis in cells. We showed by this system that HIV- 1 Vpr is a strong inducer of apoptosis, and that Vpr displays no detectable anti-apoptotic action.
In conclusion, we have made great progress in understanding the biology of HIV-1 Nef and Vpr. It is much clearer that the detaild studies on the functions in vivo of HIV-1 Nef and Vpr is required.
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