2018 Fiscal Year Final Research Report
Molecular mechanism of APOBEC3-mediated inhibition on Gag-Pol autoprocessing
| Project/Area Number |
16K08821
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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 | Kindai University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
宮澤 正顯 近畿大学, 医学部, 教授 (60167757)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | Retrovirus / MuLV / HIV-1 / APOBEC3 / 感染抵抗性因子 / Gag-Pol autoprocessing / Gag assembly |
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| Outline of Final Research Achievements |
APOBEC3 is a cytidine deaminase and inhibits the replication of various types of viruses through the deaminase-dependent and -independent ways. Understanding the entire mechanisms that underlie the anti-viral function of APOBEC3 remains incomplete. Here, we investigated how APOBEC3 interferes with the replication of human immunodeficiency virus (HIV-1) and murine leukemia viruses (MuLVs). We found that APOBEC3 binds Gag-Pol precursor polyprotein and interferes with the production of mature viral protease (PR) autoprocessed from the Gag-Pol precursor, leading to an increase in immature virus particles, which can not infect with cells. Our results suggest that this inhibitory effect of APOBEC3 is independent on its deaminase activity and probably mediated through the promotion of aberrant digestion of Gag-Pol. We also found that APOBEC3 may reduce virion production likely through the binding to Gag-Pol and subsequent inhibition of virion assembly.
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| Free Research Field |
ウイルス学
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| Academic Significance and Societal Importance of the Research Achievements |
APOBEC3がこれまでに報告されている知見とは全く異なる働き方（分子機序）をすることでウイルス複製を抑制していると明らかにした点、本研究の学術的意義がある。また、本研究により明らかになった分子機序が様々な病原微生物にも働く可能性があり、感染症分野に広く影響を及ぼす成果である。長期にわたり感染症制圧を達成するには薬剤耐性ウイルス等の脅威に備えなければならず、そのための新薬開発は社会的要求度が高い。本研究成果は「HIV-1などのレトロウイルスに対して新たな作用機序を持つ新規抗ウイルス薬の開発」に結びつく社会的意義がある。
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