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.

项目摘要/摘要 慢性乙型肝炎病毒感染影响了全球约3.5亿人，构成了 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已被证明会诱导线粒体（线粒体）自噬。 帕金转移到线粒体。我们建议研究线粒体之间的可能联系 HBV和先天免疫引起的动力学。 HBV残废 慢性持续感染。在这里，我们建议研究HBV-的分子机制 从线粒体平台诱导了抑制先天免疫信号传导。关键球员 过程是线粒体抗病毒信号传导蛋白（MAV）。有足够的支持 信息表明，帕金（E3）泛素连接酶与线粒体上的小牛相互作用 帕金引起了小牛的泛素化。这些调查将阐明MAV的方式 由帕金（Parkin 合成。这些相互作用和泛素化最终削弱了先天的免疫力。这些研究 将提供对HBV诱导的线粒体动力学的分子机制的独特见解和 它对改变宿主先天免疫反应和开放新调查途径的影响 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