| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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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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