2019 Fiscal Year Final Research Report
Elcidating the regulatory mechanisms of intracellular level and function of HIV-1 Vif
| Project/Area Number |
16K08807
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Kyoto University |
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Principal Investigator |
Shindo Keisuke 京都大学, 医学研究科, 特定病院助教 (10602344)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Keywords | HIV-1 / Vif / CBF-beta / PP2A / MDM2 / anti-HIV drug / cell cycle arrest |
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| Outline of Final Research Achievements |
I have made two major achievements in the research on HIV-1 Vif.
First, I have elucidated that CBF-beta maintains intracellular levels of Vif protein mainly by suppressing MDM2-meidated degradation of Vif, suggesting higher probability of success for developing a new anti-HIV-1 drug that prevents interaction between Vif and CBF-beta.
Second, I have proposed and proved that HIV-1 Vif triggers G2 cell cycle arrest by ubiquitinating and promoting degradation of PP2A-B56 family proteins. These contribute to elucidate not only mechanisms of pathogenesis and replication augmentation of HIV-1, but also general regulation mechanisms of cell cycle.
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| Free Research Field |
血液・ウイルス
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果の学術的意義としては、HIV-1感染症の新規治療薬の開発を支持するものと、病原性発揮や感染性増強のメカニズムを明らかにするものがあげられる。既存のすべてのHIV-1感染症治療薬に対して、それに耐性を示すウイルス変異が同定されている。VifはHIV-1 の感染に必須のウイルス蛋白でありながら、その機能発現には決まった宿主蛋白との相互作用が必須であり、そこを標的とする抗ウイルス薬に対して生じた耐性変異はVif機能を失うことが予想され、薬剤耐性ウイルスを生じないと考えられる。
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