2004 Fiscal Year Final Research Report Summary
Functional domain analysis of HIV accessory proteins
| Project/Area Number |
14370103
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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, 大学院・ヘルスバイオサイエンス研究部, 教授 (90127043)
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| Co-Investigator(Kenkyū-buntansha) |
KOYAMA Hajime Wakayama Medical University, Professor, 教授 (80109074)
UCHIYAMA Tsuneo The University of Tokushima, Graduate School Institute of Health Biosciences, Associate Professor, 大学院・ヘルスバイオサイエンス研究部, 助教授 (90151901)
FUJITA Mikako The University of Tokushima, Graduate School Institute of Health Biosciences, Assistant Professor, 大学院・ヘルスバイオサイエンス研究部, 助手 (00322256)
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| Project Period (FY) |
2002 – 2004
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| Keywords | HIV-1 / HIV-2 / Vif / Nef / Vpr / Vpx / proteasome-degradation |
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| Research Abstract |
In this study, we have done functional domain analyses on Vif and Nef of HIV-1, and also on Vpx and Vpr of HIV-2. Results obtained can be summarized as follows. (1) HIV-1 Vif. By comparing the activities of Vif from long term nonprogressors and progressors for AIDS, we found that Vif could influence HIV-1 infectivity and disease progression in infected individuals. We have constructed a series of HIV-1 Vif mutants in vitro, and have characterized them biologically and biochemically. During the course of this mutational analysis, we noticed that HIV-1 Vif is extremely and uniquely sensitive to proteasome-degradation among HIV accessory proteins. We identified the lysine residues responsible for this degradation, and showed that it is critically important for the optimal infectivity of HIV-1. (2) HIV-1 Nef. By using a point mutant of Nef which is defective only for MHC-I down-regulation, we have demonstrated that HIV-1 Nef suppresses the cytokine production by CTL cells only partially, while completely their cytocydial activity. (3) HIV-2 Vpx and Vpr. In additoin to Vpr, which is also encoded by the genome of HIV, HIV-2 carries Vpx in its genome. By homology modeling, it has been clearly and strongly suggested that HIV-1 Vpr, HIV-2 Vpx and HIV-2 Vpr are structurally very similar, having three or four major helices. In our functional mutational study, HIV-2 Vpx and Vpr were found to have more functions than HIV-1 Vpr such as enhancing reverse transcription of viral genome and augmenting virion release.
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[Journal Article] High level expression of Human Immunodeficiency Virus type-1 Vif inhibits viral infectivity by modulating proteolytic processing of the Gag precursor at the p2/NC processing site.2004
Author(s)
Akari, H., Fujita, M., Kao, S., Khan, M.A., Shehu-Xhilaga, M., Adachi, A., Strebel, K.
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Journal Title
Journal of Biological Chemistry 279
Pages: 12355-12362
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression of HIV-1 accessory protein Vif is controlled uniquely to be low and optimal by proteasome-degradation.2004
Author(s)
Fujita, M., Akari, H., Sakurai, A., Yoshida, A., Chiba, T., Tanaka, K., Strebel, K., Adachi, A.
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Journal Title
Microbes and Infection 6
Pages: 791-798
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Functional analysis of HIV-1 vif genes derived from Japanese long-term nonprogressors and progressors for AIDS.2004
Author(s)
Sakurai, A., Jere, A., Yoshida, A., Yamada, T., Iwamoto, A., Adachi, A., Fujita, M.
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Journal Title
Microbes and Infection 6
Pages: 799-805
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Determination of HIV-1 infecivity by lymphocytic cell lines with integrated luciferase gene.2004
Author(s)
Nagao, T., Yoshida, A., Sakurai, A., Piroozmand, A., Jere, A., Fujita, M., Uchiyama, T., Adachi, A.
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Journal Title
International Journal of Molecular Medicine 14
Pages: 1073-1076
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Generation and characterization of HIV-1 clones chimeric for subtypes B and C nef.2004
Author(s)
Jere, A., Piroozmand, A., Tripathy, S., Paranjape, R., Sakurai, A., Fujita, M., Adachi, A.
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Journal Title
International Journal of Molecular Medicine 14
Pages: 1087-1090
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Amino acid residues 88 and 89 in the central hydrophilic region of human immunodeficiency virus type 1 Vif are critical for viral infectivity by enhancing the steady-state expression of Vif.2003
Author(s)
Fujita, M., Sakurai, A., Yoshida, A., Miyaura, M., Koyama, A.H., Sakai, K., Adachi, A.
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Journal Title
Journal of Virology 77
Pages: 1626-1632
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Susceptibility of HVS-immortalized lymphocytic HSC-F cells to various strains and mutants of HIV-SIV.2003
Author(s)
Fujita, M., Yoshida, A., Sakurai, A., Tatsuki, J., Ueno, F., Akari, H., Adachi, A.
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Journal Title
International Journal of Molecular Medicine 11
Pages: 641-644
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Vpx and Vpr proteins of HIV-2 up-regulate the viral infectivity by a distinct mechanism in lymphocytic cells.2003
Author(s)
Ueno, F., Shiota, H., Miyaura, M., Yoshida, A., Sakurai, A., Tatsuki J., Koyama, A.H., Akari, H., Adachi, A., Fujita, M.
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Journal Title
Microbes and Infection 5
Pages: 387-395
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Subtle mutations in the cysteine region of HIV-1 Vif drastically alter the viral replication phenotype.2002
Author(s)
Fujita, M., Sakurai, A., Yoshida, A., Matsumoto, S., Miyaura, M., Adachi, A.
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Journal Title
Microbes and Infection 4
Pages: 621-624
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Apparent lack of trans-dominant negative effects of various vif mutants on the replication of HIV-1.2002
Author(s)
Fujita, M., Matsumoto, S., Sakurai, A., Doi, N., Miyaura, M., Yoshida, A., Adachi, A.
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Journal Title
Microbes and Infection 4
Pages: 1203-1207
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Unique characteristics of HIV-1 Vif expression.
Author(s)
Wang, H., Sakurai, A., Khamsri, B., Uchiyama, T., Gu, H., Adachi A, Fujita, M.
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Journal Title
Microbes and Infection (in press)
Description
「研究成果報告書概要(欧文)」より
