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Mechanisms of HBV-Induced Innate Immunity

乙型肝炎病毒诱导的先天免疫机制

基本信息

批准号：
9513990
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
项目类别：
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/9513990
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 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 Pathway interactions 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 insight liver injury mitochondrial autophagy novel parkin gene/protein protein function recruit therapeutic target ubiquitin-protein ligase

项目摘要

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.

项目总结/文摘