Identification of novel anti-hepatitis B virus defense mechanisms
| Project/Area Number |
18590731
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Kyoto University |
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Principal Investigator |
MARUSAWA Hiroyuki Kyoto University, Graduate School of Medicine, Department of Gastroenterology and Hepatology, Assistant professor (80324630)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | hepatitis B virus / APOBEC3G / HepG2 cell / HBV / APOBEC / 遺伝子変異 / 肝細胞 / HBe抗原 / 遺伝子編集酵素 / B型肝炎 / 感染モデル / HepG2 / 免疫応答 / 抗ウィルス分子 |
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| Research Abstract |
In this study, we tried to identify the novel anti-hepatitis B virus (HBV) defense mechanisms in the infected hepatocytes, and the following results were obtained. We first established a culture model of a hepatoma-derived cell line that supports the infection and replication of HBV. For this purpose, HepG2 cells were exposed to 2% DMSO in the presence or absence of 4% PEG and subsequently examined for their susceptibility to HBV infection using the HBV-DNA positive serum of HBV asymptomatic careers. We found that DMSO alone did not enhance the HBV infection of HepG2 cells. However, treatment with DMSO plus PEG resulted in a marked enhancement of HBV replication in HepG2 cells, indicating that DMSO administered with PEG renders HepG2 cells susceptible to infection by HBV that originates from the sera of HBV-infected patients, and allows the replication of this virus. Using this in vitro infection model, we analyzed the expression profiles of various genes in HBV-infected hepatocytes, and identified APOBEC3G as a HBV infection-inducible host gene. To investigate the anti-HBV activity of APOBEC3G, we tested whether APOBEC3G inhibits viral replication in HepG2 cells infected with serum-derived HBV. We detected substantial levels of HBV DNA synthesis in the control HepG2 cells seven days after infection with HBV. In contrast, cells expressing either exogenous wild-type or mutant APOBEC3G had levels of HBV DNA significantly lower than those of the control cells. Moreover, a number of DNA mutations were detected in HBV genomes derived from cells that expressed APOBEC3G. Taken together, these data indicate that the anti-HBV activity of APOBEC3G might be attributable to two different mechanisms : an inhibitory effect on HBV DNA synthesis, and an editing activity that generates DNA mutations in the viral genome.
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Report
(3 results)
Research Products
(4 results)
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[Journal Article] Anti-viral protein APOBEC3G is induced by interferon-alfa stimulation in human hepatocytes2006
Author(s)
Tanaka, Y., Marusawa, H., Seno, H., Matusmoto, Y., Ueda, Y., Kodama, Y., Endo, Y., Yamauchi, J., Matsumoto, T., Takaori-Kondo, A., Ikai, I., Chiba, T
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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