Regulation of HIV replication by proteasome degradation of Vif
| Project/Area Number |
15590420
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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 | The University of Tokushima |
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Principal Investigator |
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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| Co-Investigator(Kenkyū-buntansha) |
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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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | HIV-1 / accessory protein / Vif / proteasome degradation / viral replication / ubiquitination / Cullin / lysine / アルギニン |
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| Research Abstract |
An objective of this study is to elucidate regulation of HIV-1 replication by proteasome-degradation of accessory protein Vif. We have been trying to reveal (1)mechanism of the degradation (2)regulation mechanism of magnitude of the degradation (3)biological significance of the degradation on viral replication, and gotten the following results.
(1)Proteasome degradation of Vif was analyzed biochemically by pulse/chase experiments. Two forms of Vif, cytosolic and cytoskeletal, have been known. Cytoskeletal Vif was found to be more stable than soluble cytosolic Vif, and accumulate with time. The degradation characteristics of Vif were cell type-independent and observed in both non-permissive and permissive cells. Comparative stability analysis of the four HIV-1 accessory proteins were performed. Vif was unique in its short half-life and in the degradation. We monitored Vif ubiquitination by immunoprecipitation/Western blotting system. Futhermore, interaction of Vif with Cullin was observed by immunoprecipitation, suggesting the possibility that Cullin works as ubiquitin ligase. (2)Characterization of a series of vif deletion mutants showed that amino acids predicted to be important for formation of β-strand structures (amino acid nos.63-70 and 86-89) were critical for maintaining a normal expression level of Vif and for viral infectivity. (3)Vif mutant, in which all 16 lysines were changed to arginines, was found to be extremely high expression level compared with wild type, and not to confer replication ability on virus. However, we showed that the lack of function was caused by the critical role of 22^<nd> and 26^<th> lysines on viral infectivity, suggesting that arginine mutants are not useful to elucidate biological significance of the degradation on viral replication.
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Unique characteristics of HIV-1 Vif expression.2005
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 7
Pages: 385-390
Description
「研究成果報告書概要(欧文)」より
Related Report
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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
Related Report
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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
Related Report
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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
Related Report
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