| Project/Area Number |
18K08460
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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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| Review Section |
Basic Section 54030:Infectious disease medicine-related
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| Research Institution | National Center for Global Health and Medicine |
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Principal Investigator |
Higashi-Kuwata Nobuyo 国立研究開発法人国立国際医療研究センター, その他部局等, 研究所 難治性ウイルス感染症研究部 主任研究員 (60361218)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | HBV感染 / HBV感染と細胞老化 / 抗HBV核酸アナログと細胞老化 / 抗HBV核酸アナログと細胞老化細胞老化 / 老化関連βガラクトシダーゼ / p21 / 細胞老化 / 抗HBV核酸アナログ / 老化関連β-ガラクトシダーゼ / p16 / テロメア長 / SASP |
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| Outline of Final Research Achievements |
While certain nucleoside/nucleotide analogs are effective in the treatment of HBV infections, their efficacy and safety are yet to be optimized due to life-long medication period. We have designed, synthesized, and identified multiple novel nucleoside/nucleotide analogs. However, the effects of long-term administration of these nucleic acid analogs and HBV infection itself on HBV-infected hepatocytes have not yet been well evaluated. In this study, we revealed that HBV infection causes a decrease in nuclear localization of senescence-related protein p21 in HBV infected cells compared to non-infected cells, and its cellular senescence retrograde phenomenon tends to be corrected to normal levels by administration of a novel nucleoside analog, E-CFCP.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究ではHBV感染細胞では非感染細胞に比して老化関連タンパクp21の核内局在低下が惹起される事、更にその感染細胞での核内局在は 添加する抗HBV核酸アナログ種により異なって変動する事を見出した。加えて感染細胞でのp21核内局在低下（細胞老化逆行）現象は新規核酸アナログ, E-CFCPの添加/投与により正常細胞レベルに戻る傾向がある事を明らかにした。この是正効果が核酸アナログの直接的抗ウイルス活性のみに因るものか今後も検討が必要ではあるが、その様な検討を通じHBV複製を強力に抑制し、細胞機能を病態改善に有利に修飾（HBV感染症では肝癌化阻止）も可能な、より有望な薬剤創出に有用なデータを供する。
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