2017 Fiscal Year Final Research Report
Integrating multiple omics analysis for understanding the pathological mechanism of chronic hepatitis B virus infection and identifying potential molecular targets using humanized chimeric mice
| Project/Area Number |
15K06810
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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 |
Laboratory animal science
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | B型肝炎 / B型肝炎ウイルス / ヒト化肝臓キメラマウス / トランスクリプトーム解析 |
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| Outline of Final Research Achievements |
Nucleos(t)ide analogues, the standard of care for chronic hepatitis B virus (HBV) infection, cannot eliminate the virus completely from HBV-infected hepatocytes. Therefore, novel agents with different antiviral actions are needed. We have established a humanized liver-chimeric mouse model at a relatively low cost. Using this model, we performed comprehensive transcriptome analyses of liver tissues from the hyperacute phase to the chronic infection phase. Surprisingly, there was a much higher number of weakly expressed mRNAs than of strongly expressed mRNAs. Three miRNAs were consistently upregulated during this period. Inhibitors of these miRNAs reduced the efficiency of HBV infection and replication. Some mRNAs that specifically interacted with these miRNAs affected the chronicity of the infection. Proteomic and metabolomic analyses showed elevated lipoprotein-related concentrations. HBV is suggested to adapt host circumstances by stealth nature against the host innate immune system.
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| Free Research Field |
肝臓病学
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