Mechanisms of HBV-Induced Innate Immunity

乙型肝炎病毒诱导的先天免疫机制

• 批准号: 10159072
• 负责人: ALEEM SIDDIQUI
• 金额: $ 38.75万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-23 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10159072
• 关键词: Affect; Antiviral Agents; Apoptosis; Apoptotic; Applications Grants; Attenuated; Cell Death; Cell Maintenance; Chronic; Chronic Hepatitis; Chronic Hepatitis B; Complex; Data; Dynamin; Event; Excision; Fibrosis; Gene Expression; Genes; Goals; Hepatitis B; Hepatitis B Virus; Homeostasis; Human; Immune signaling; Injury; Innate Immune Response; Interferons; Investigation; Lead; Link; Liver Mitochondria; Liver diseases; Lysine; Maintenance; Mediating; Mediator of activation protein; Metabolic; Mitochondria; Molecular; Natural Immunity; Oxidative Stress; PINK1 gene; Parkinson Disease; Pathogenesis; Phosphorylation; Phosphotransferases; Physiological; Play; Primary carcinoma of the liver cells; Process; Production; Proteins; Publishing; Receptor Signaling; Risk Factors; Role; Signal Transduction; Signaling Molecule; Signaling Protein; TNF receptor-associated factor 3; Tretinoin; Ubiquitination; Virus Diseases; Work; chronic infection; chronic liver injury; cytochrome c; innate immune pathways; insight; liver injury; mitochondrial autophagy; novel; parkin gene/protein; protein function; recruit; therapeutic target; ubiquitin-protein ligase

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.

项目概要/摘要 慢性乙型肝炎病毒感染影响全球约 3.5 亿人，并构成 纤维化和肝细胞癌（HCC）的重要危险因素。乙型肝炎病毒改变线粒体 动力学。乙型肝炎病毒已被证明可诱导线粒体自噬（Mitophagy），如下所示： 帕金易位至线粒体。我们建议研究线粒体之间可能的联系 HBV 和先天免疫诱导的动态变化。乙型肝炎病毒会削弱宿主的先天免疫力以维持 慢性持续感染。在这里，我们建议研究 HBV-的分子机制。 诱导抑制线粒体平台的先天免疫信号。这其中的关键人物 过程是线粒体抗病毒信号蛋白（MAVS）。有足够的支撑 信息显示 Parkin（一种 E3 泛素连接酶）与线粒体上的 MAVS 相互作用 Parkin 会导致 MAVS 泛素化。这些调查将阐明 MAVS 是如何 超复合物中的 Parkin 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会削弱先天免疫。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。

项目成果

Monitoring Mitochondrial Function in Aedes albopictus C6/36 Cell Line during Dengue Virus Infection.

• DOI: 10.3390/insects12100934
• 发表时间: 2021-10-14
• 期刊: Insects
• 影响因子: 3
• 作者: Santana-Román ME;Maycotte P;Uribe-Carvajal S;Uribe-Alvarez C;Alvarado-Medina N;Khan M;Siddiqui A;Pando-Robles V
• 通讯作者: Pando-Robles V

The role of N6-methyladenosine modification in the life cycle and disease pathogenesis of hepatitis B and C viruses.

• DOI: 10.1038/s12276-021-00581-3
• 发表时间: 2021-03
• 期刊: Experimental & molecular medicine
• 影响因子: 12.8
• 作者: Kim GW;Siddiqui A
• 通讯作者: Siddiqui A