Mechanisms of HBV-Induced Innate Immunity

项目概要/摘要 慢性B型肝炎病毒感染影响全世界约3.5亿人，并构成一个全球性的疾病。 纤维化和肝细胞癌（HCC）的重要危险因素。HBV改变线粒体 动力学HBV已显示诱导线粒体的自噬（线粒体自噬），如以下所证明的： 帕金易位到线粒体。我们建议调查线粒体和线粒体之间的可能联系， HBV和先天免疫诱导的动力学。HBV削弱宿主的先天免疫力， 慢性持续性感染在这里，我们建议研究HBV的分子机制- 诱导抑制来自线粒体平台的先天免疫信号传导。其中的关键人物 该过程是线粒体抗病毒信号蛋白（MAVS）。有足够的支持 信息，这表明Parkin，一种E3泛素连接酶，与线粒体上的MAVS相互作用 帕金导致了MAVS的泛素化。这些调查将阐明MAVS是如何 在超复合体中被帕金靶向并影响干扰素的下游抗病毒信号传导 合成.这些相互作用和泛素化最终削弱了先天免疫。这些研究 将为HBV诱导的线粒体动力学的分子机制提供独特的见解， 它对改变宿主先天免疫反应的影响，并开辟了新的研究途径， 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.