| 研究実績の概要 |
Although HBV does not cause significant induction of the innate immune system both in vivo and in vitro, 90% of HBV infected ad ult patients can clear the virus. These data suggest the presence of other interferon-independent pathways that can suppress HBV . We aim to identify these pathways at both the transcriptional and post transcriptional levels (RNA degradation). In the last fiscal year Marwa has identified MafF as a negative regulator of HBV-RNA (PgRNA). She also analyzed the expression o f MafF in chronic HBV patients, and showed a higher expression of MafF in these patients compared to control non-infected subjects. These data predict an important function of MafF in HBV infection especially on the ratio between HBV-RNA transcription/Degradation. .
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
She arrived to our laboratory in September. In 6 months, she get accustomed to the laboratory, and has identified MafF as a major regulator of HBV-RNA titer in the cells. MafF effect on suppressing HBV is pangenotypic, suggesting its importance as a new anti-HBV host factor. Project is working smoothly, and I predict she will identify the mechanism of action for MafF next year.
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| 今後の研究の推進方策 |
In this Fiscal year she will work on identifying the mechanism by which MafF suppress HBV-RNA. The suppressive effect of MafF on HBV-RNA may be mediated by the suppression of transcription from HBV promoters, or the induction of HBV-RNA degradation. The effect of MafF on the different HBV promoters will be identified using promoter reporter system. Furthermore its direct interaction with HBV promoters will also be analyzed by CHIP assay. The effect of MafF on the induction of RNA-degradation will be also analyzed by northern blot analysis. Also its suppressive effect on different stages on HBV life cycle will also be confirmed by detecting HBV-DNA (southern-blot) RNA (Northern Blot), Proteins Western Blot. In the case MafF has an anti-viral function, it may be induced by virus infection, or by inflammatory mediators. The induction of MafF expression and the mechanism of this induction either by virus infection, TLR stimulation, or by inflammatory cytokines will be investigated. In case an inducer is identified, the mechanism by which this inducer can affect MafF ex pression will be investigated, first by analyzing reported pathways, or by performing molecular biology experiments like protein /protein interaction, and loss of function analysis. The effect of MafF on HBV-RNA and infection in vivo will be also analyzed u sing hydrodynamic injection of MafF and HBV
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