Mechanisms of HBV-Induced Innate Immunity

项目摘要/摘要 慢性乙肝病毒感染影响着全球约3.5亿人，并构成 肝纤维化和肝细胞癌的重要危险因素。乙肝病毒改变线粒体 动力学。乙肝病毒已被证明可以诱导线粒体的自噬(有丝分裂)，这是由 帕金易位到线粒体。我们建议调查线粒体之间可能存在的联系 乙肝病毒和先天免疫诱导的动态变化。乙肝病毒削弱宿主天然免疫力以维持 慢性持续性感染。在这里，我们建议研究乙肝病毒的分子机制。 诱导抑制线粒体平台的先天免疫信号。这件事的关键人物 Process是一种线粒体抗病毒信号蛋白(MAV)。有足够的支持 信息显示，Parkin，一种E3泛素连接酶，与线粒体上的MAV相互作用 帕金导致了小牛的泛素化。这些调查将阐明小牛是如何 Parkin在超复合体中靶向并影响干扰素的下游抗病毒信号 综合。这些相互作用和泛素化最终会削弱先天免疫力。这些研究 将对乙肝病毒诱导的线粒体动力学和分子机制提供独特的见解 其在改变宿主先天免疫反应中的作用和开辟新的研究途径 阐明先天免疫途径。

Project Summary/Abstract Chronic Hepatitis B virus infections affect about 350 million people worldwide and constitute a significant risk factor for fibrosis and hepatocellular carcinoma (HCC). HBV alters mitochondrial dynamics. HBV has been shown to induce autophagy of mitochondria (Mitophagy) as evidenced by Parkin translocation to mitochondria. We propose to investigate a possible link between mitochondrial dynamics induced by HBV and innate immunity. HBV cripples host innate immunity to maintain chronic persistent infection. Here, we propose to investigate the molecular mechanisms of HBV- induced suppression of innate immune signaling from mitochondrial platform. The key player in this process is a mitochondrial antiviral signaling protein (MAVS). There is sufficient supporting information, which shows that Parkin, an E3 ubiquitin ligase, interacts with MAVS on the mitochondria and that Parkin causes the ubiquitination of MAVS. These investigations will elucidate how MAVS is targeted by Parkin in a supracomplex and affects downstream antiviral signaling of interferon synthesis. These interactions and ubiquitinations eventually cripple innate immunity. These studies will provide unique insights into molecular mechanisms of HBV-induced mitochondrial dynamics and its effects on altering host innate immune response and open new avenues of investigations in the elucidation of innate immune pathways.