The Biophysics of Virus Capsid Assembly

病毒衣壳组装的生物物理学

基本信息

批准号：
8880573
负责人：
Adam Zlotnick
金额：
$ 34.73万
依托单位：
TRUSTEES OF INDIANA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8880573
关键词：
Affect Allosteric Regulation Antiviral Agents Binding Biological Biology Biophysics Capsid Cell Culture Techniques Cell Nucleus Cells Cessation of life Chromosomes Chronic Chronic Hepatitis B Circular DNA Cirrhosis Complex Core Assembly Core Protein Cytoplasm DNA DNA Viruses Data Dissociation Elements Epigenetic Process Funding Genetic Transcription Genome Health Hepatitis B Virus Human Importins In Vitro Infection Infectious hepatitides Length Life Cycle Stages Liver Failure Membrane Proteins Messenger RNA Metabolic Molecular Molecular Chaperones Morbidity - disease rate Nuclear Nucleic Acids Phosphotransferases Physics Play Primary carcinoma of the liver cells Property Protein Kinase Proteins RNA RNA Splicing RNA-Directed DNA Polymerase Reverse Transcription Role Signal Transduction Source Staging Structure Testing Therapeutic Viral Virus Virus Diseases Virus Replication Work base biological systems biophysical properties dimer mortality mutant response synergism trafficking viral RNA virus core

项目摘要

DESCRIPTION (provided by applicant): Hepatitis B virus (HBV) is a major cause of morbidity and mortality, worldwide. About 350 million people suffer from chronic HBV and about 600,000 die from its sequellae annually. HBV is an enveloped virus with an icosahedral core that also functions as a metabolic compartment. Indeed, the core protein plays pleiotropic roles in many elements of HBV replication. To accomplish multiple functions we hypothesize a complex allosteric regulation of the protein and the assembled core. We will study assembly of empty cores and correlate that with assembly of cores on nucleic acid substrates. We will examine assembly of cores on nucleic acid substrates and correlate that with reverse transcription. Our preliminary data indicates that the core plays an active role in reverse transcription; it is much more than a passive container. We will correlate the synergism between core structure and reverse transcription with intracellular localization of core. By emphasizing the structural basis f these correlations, we will define the mechanisms relating assembly, reverse transcription of viral RNA, and core trafficking within a cell. In the last few years, the HBV core protein has emerged as a target for antiviral therapeutics. The studies described in our proposal will serve as a basis for defining molecular mechanisms of such antiviral molecules.

描述（由申请人提供）：乙型肝炎病毒（HBV）是全世界发病和死亡的主要原因。每年约有 3.5 亿人患有慢性乙型肝炎，约 60 万人死于其后遗症。乙型肝炎病毒是一种具有二十面体核心的包膜病毒，也具有代谢区室的功能。事实上，核心蛋白在 HBV 复制的许多元件中发挥多效性作用。为了实现多种功能，我们假设蛋白质和组装核心存在复杂的变构调节。我们将研究空核心的组装，并将其与核酸基质上的核心组装相关联。我们将检查核酸底物上核心的组装，并将其与逆转录相关联。我们的初步数据表明核心在逆转录中发挥着积极的作用；它不仅仅是一个被动的容器。我们将把核心结构和逆转录之间的协同作用与核心的细胞内定位联系起来。通过强调这些相关性的结构基础，我们将定义与组装、病毒 RNA 逆转录和细胞内核心运输相关的机制。在过去几年中，乙型肝炎核心蛋白已成为抗病毒治疗的靶点。我们提案中描述的研究将作为定义此类抗病毒分子的分子机制的基础。