权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

How MERS-CoV Regulates Immunity in Human Lung Tissue

MERS-CoV 如何调节人肺组织的免疫力

基本信息

批准号：
10187973
负责人：
AMY C SIMS
金额：
$ 16.69万
依托单位：
BATTELLE PACIFIC NORTHWEST LABORATORIES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-05 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10187973
关键词：
Acetylation Antibodies Antiviral Agents Architecture Area Binding Cell Culture Techniques Cell Line Cells Chromatin Chromatin Structure Complex Consensus Coronavirus Coronavirus Infections DNA Methylation Data Data Set Development Disease Outcome Emerging Communicable Diseases Endothelial Cells Endothelium Enzymes Epigenetic Process Epithelial Cells Fibroblasts Foundations Future Gene Expression Gene Expression Profile Gene Expression Regulation Genes Goals Histone Deacetylase Histones Human IRF3 gene Immune Immune response Immunity Infection Innate Immune Response Interferon-beta Interferons Kinetics Lung Mediating Methods Methylation Middle East Respiratory Syndrome Coronavirus Modeling Modification Molecular Natural Immunity Pathogenesis Pathogenicity Pathway interactions Pattern Play Primary Infection Process Promoter Regions Proteins Proteomics Public Health RNA Readiness Role STAT1 gene Severity of illness Structure of parenchyma of lung Testing Therapeutic Tissues Vaccines Viral Viral Genes Viral Proteins Virus Virus Diseases Virus Replication airway epithelium base cell type chromatin immunoprecipitation chromatin modification chromatin remodeling cytokine design differential expression disease phenotype epigenome histone methylation histone methyltransferase human coronavirus immune activation improved inhibitor/antagonist insight novel novel coronavirus novel strategies novel virus pathogen prevent programs respiratory respiratory virus response tissue regeneration tissue repair transcription factor transcriptomics

项目摘要

ABSTRACT The molecular mechanisms regulating emerging highly pathogenic human respiratory coronavirus pathogenesis are complex and include dampening of the host innate immune response allowing higher viral titers immediately following entry. Previous studies tracking the expression of interferon stimulated gene (ISG) expression in Middle East respiratory syndrome coronavirus (MERS-CoV) infected continuous human lung epithelial cells demonstrated that specific ISG expression patterns could be detected and these patterns could be used to determine how CoV were modulating the innate immune response. Epigenetic/chromatin remodeling mechanisms were found to be important regulators of host chromatin remodeling that altered host expression ISG patterns. This proposal will build on these foundational studies performed in continuous human lung cell lines and define ways that MERS-CoV regulates innate immunity in primary human lung fibroblasts and microvascular endothelial cells.

摘要新出现的高致病性人类呼吸道疾病的分子调控机制冠状病毒的发病机制是复杂的，包括抑制宿主的先天免疫在进入后立即产生允许更高病毒滴度的应答。以前的研究跟踪了中东呼吸综合征患者干扰素刺激基因（ISG）的表达冠状病毒（MERS-CoV）感染的连续人肺上皮细胞证明，可以检测特定的ISG表达模式，这些模式可以用于确定冠状病毒如何调节先天免疫反应。表观遗传/染色质重塑机制被认为是宿主染色质重塑的重要调节因子改变了宿主表达ISG模式。这项建议将建立在这些基础研究的基础上在连续的人肺细胞系中进行，并确定MERS-CoV调节原代人肺成纤维细胞和微血管内皮细胞的先天免疫。