2019 Fiscal Year Research-status Report
DOCK11ノックダウンによりcccDNA排除の新規抗HBV治療応用への基礎研究
| Project/Area Number |
18K07966
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| Research Institution | Kanazawa University |
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Principal Investigator |
李 影奕 金沢大学, 医学系, 博士研究員 (70401940)
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| Co-Investigator(Kenkyū-buntansha) |
本多 政夫 金沢大学, 保健学系, 教授 (00272980)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | Hepatitis B virus / cccDNA / Dock11 / infection |
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| Outline of Annual Research Achievements |
【Purpose】 The purpose of this project is to understand the roles of DOCK11 in cccDNA maintenance and subsequently clarify the possibility of DOCK11 as a target molecule for treating chronic HBV infection. Last year, we have realized that HBV DNA could entry to the nucleus by Dock11 regulating X gene. 【Summary the results through 2019.4.1 to 2020.3.31】This Year, we uncover the new trafficking of Hepatitis B virus by Dock11 regulating X gene and having the interaction with Y gene in the HepG2-NTCP-C4 cells. Moreover, the mouse experiment was performed, which indicated the Knocked down of Dock11 might prevent the recycling and maintenance of cccDNA in vivo.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The project is going smoothly according to the experimental plan. The biological effects and mechanism of DOCK11 regarding HBV DNA maintenance were investigated in vitro and in vivo.
1)We identified the new trafficking pathway of Hepatitis B virus entering to the nucleus by Dock11 regulating. In another words, this trafficking pathway might serve as recycling of Hepatitis B virus.
2)Some inhibitor of this trafficking pathway could inhibit the Hepatitis B virus entering to nucleus by Immunofluorescence analysis, HBc ELISA assay, and cccDNA analysis.
3)The expression of X gene was regulated by Dock11. The expression of Dock11 and X gene might control the expression and activity of Y gene, eventually let Hepatitis B virus into nucleus to recycle them.
4)The cccDNA maintenance was also prevented by knocking down of Dock11 in vivo.
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| Strategy for Future Research Activity |
We will perform the experiment according to the research plan.
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