Offer insight the mechanism of hepatitis B virus elimination by a novel regulated cell death type: ferroptosis.
| Project/Area Number |
22K16033
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
闕 路晟 国立感染症研究所, ウイルス第二部, 研究員 (20941636)
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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2024: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | HBV / Ferroptosis / infected / clearance / ferroptosis |
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| Outline of Research at the Start |
Hepatitis B virus is a causative agent of serious liver illness. Current antiviral drugs have failed to eradicate infected cells. Focusing on a novel type of cell death, the mechanism how HBV and host immune response sensitize the infected cells to ferroptosis will be investigated.
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| Outline of Annual Research Achievements |
We discovered that HBV infection can influence the expression of certain genes related to ferroptosis in both HBV-infected and uninfected groups. In 2023, our goal is to explore the role of these genes in HBV infection. Using a loss-of-function approach with siRNA, we observed that reducing a ferroptosis biomarker in an HBV-infected cell line (NTCP-HepG2) led to the following results: 1) a slight increase in cell viability; 2) a decrease in HBV markers such as HBV DNA, HBsAg, and HBeAg. Subsequently, we used an inhibitor targeting a ferroptosis biomarker to validate the siRNA results, which showed similar trends. Additionally, the phenotypic detection of ferroptosis indicated that the siRNA-transfected group exhibited a significant decrease in lipid ROS compared to the NC group.
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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
As indicated in the research summary, progress for the second year is generally on track.
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| Strategy for Future Research Activity |
In 2024, our goal is to comprehend the function of this gene in living organisms. To achieve this, we will use the hydrodynamic injection (HDI) HBV replication mice model. We will deliver either the siRNA or the inhibitor of the target gene. Subsequently, we will quantify markers of ferroptosis and HBV infection to the HDI HBV to gain a better understanding of the role of this gene.
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Report
(2 results)
Research Products
(6 results)
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[Journal Article] Interferon-gamma induced APOBEC3B contributes to Merkel cell polyomavirus genome mutagenesis in Merkel cell carcinoma2021
Author(s)
Que L, Li Y, Dainichi T, Kukimoto I, Nishiyama T, Nakano Y, Shima K, Suzuki T, Sato Y, Horike S, Aizaki H, Watashi K, Kato T, Aly HH, Watanabe N, Kabashima K, Wakae K, Muramatsu M.
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Journal Title
J Invest Dermatol
Volume: S0022-202X(21)
Issue: 7
Pages: 02636-1
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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