HBV对固有免疫分子IFI16转录表达的抑制作用及其机制研究

干扰素诱导蛋白16（interferon-inducible protein 16，IFI16）是一重要核定位的固有免疫感受器。我们前期的工作发现IFI16可作为固有免疫识别和转录抑制的联结子有效抑制HBV cccDNA的功能，但HBV可负调IFI16的转录表达，这可能是乙肝慢性化的重要原因之一。本研究的目标在于阐明HBV抑制IFI16转录的分子机制。拟通过生信分析、缺失与定点突变、ChIP-Seq和ATAC-Seq等技术确定可能影响IFI16转录表达的顺式作用元件;通过EMSA、亲和素免疫沉淀、ChIP、Re-ChIP、BioID、过表达和CRIPR-Cas9敲除等技术确定在IFI16表达中起关键作用的转录因子以及HBV负调IFI16转录的分子机制；本课题亦将探究阻断HBV对IFI16负调作用后，对HBV cccDNA的影响。本研究将为基于IFI16抗乙肝策略提供新的理论基础与作用靶标。

Interferon-inducible protein 16,IFI16,is an important nuclear-located innate sensor. Our previous investigation found that IFI16 could inhibit the function of HBV cccDNA by intergrating the innate sensing with transcriptional suppression, however, HBV could inhibit the IFI16 transcription. In this study, we intend to dicepher the molecular mechanism by which HBV suppresses the transcription of IFI16. Bioinformatic analysis, site-directed mutagenetic analysis, ChIP-Seq and ATAC-Seq etc., will be used to determine the cis-elements responsible for IFI16 transcrption. EMSA， biotin-avidin immuneprecipitation, ChIP, ReChIP, BioID, overexpression and CRISPR-Cas9 experiments will be used to determine the transfactors responsible for IFI16 transcription, as well as to investigate the molecular mechanisms whereby HBV inhibits the transcriptional processes of IFI16. Further, we will determine whether block of the suppressive effect of HBV on IFI16 could facilitate the inhibition of HBV cccDNA funtion. This study might help provide a novel therapeutic basis for IFI16-mediated anti-HBV strategy.