P3: ROLE OF MIRNAS IN DENGUE IMMUNOPATHOGENESIS

P3：Mirnas 在登革热免疫发病机制中的作用

• 批准号: 8360755
• 负责人: Hongwei Li
• 金额: $ 21.3万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360755
• 关键词: Address; Biological Response Modifiers; Cell physiology; Culicidae; Dengue; Dengue Hemorrhagic Fever; Dengue Shock Syndrome; Dengue Virus; Developmental Process; Emerging Communicable Diseases; Extravasation; Functional RNA; Funding; Grant; Human; Infection; Infectious Diseases Research; Inflammatory; Life; MicroRNAs; Molecular; Molecular Profiling; National Center for Research Resources; Pathogenesis; Permeability; Plasma; Play; Prevention strategy; Principal Investigator; Process; Production; Regulation; Research; Research Infrastructure; Resources; Role; Source; United States National Institutes of Health; Vascular Endothelial Cell; Vascular Endothelium; Vascular Permeabilities; Virus Diseases; cost; cytokine; human disease; insight; macrophage; monocyte; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Dengue is the most prevalent mosquito-borne viral disease in humans. Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), the life-threatening forms of severe dengue virus (DENV) infection, are manifested by increased vascular permeability and plasma leakage. Available evidence indicates that infection of human monocytes/macrophages results in a dramatic increase in production of inflammatory cytokines and other immune mediators, which act on vascular endothelium and cause alteration of endothelial permeability. However, how such cellular responses are regulated and how such regulations contribute to the unique feature of DHF/DSS pathogenesis are unclear. Recently, it was demonstrated that microRNAs (miRNAs), a class of small non-coding regulatory RNAs, play important roles in most cellular and developmental processes, and deregulation of miRNA expression is associated with many human diseases. The central hypothesis of this study is that miRNAs may serve as the essential factors that modulate cellular responses of human monocytes/macrophages and vascular endothelial cells in DENV infection. To address this, miRNA expression profiling in DENV-infected monocytes/macrophages and vascular endothelial cells, and vascular endothelial cells that are treated with the immune mediators released from infected monocytes/macrophages, will be performed and analyzed. Regulatory roles of miRNAs in the pathogenic process of DHF and DSS will be further characterized. The findings from this study will help to clarify critical cellular responses in DENV infection, and provide valuable insights into the molecular mechanism of DHF immunopathogenesis. Such findings may uncover new strategies for the prevention and possibly treatment of DHF/DSS.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 登革热是人类最普遍的蚊媒病毒性疾病。登革出血热（DHF）和登革休克综合征（DSS）是严重登革病毒（DENV）感染的危及生命的形式，表现为血管通透性增加和血浆渗漏。现有证据表明，人单核细胞/巨噬细胞的感染导致炎性细胞因子和其他免疫介质的产生急剧增加，其作用于血管内皮并引起内皮通透性的改变。然而，这些细胞反应是如何调节的，以及这些调节如何促成DHF/DSS发病机制的独特特征尚不清楚。近年来研究表明，microRNA（miRNAs）是一类非编码的小分子调控RNA，在许多细胞和发育过程中发挥重要作用，并且miRNAs表达失调与许多人类疾病有关。本研究的中心假设是，miRNAs可能是调节人单核细胞/巨噬细胞和血管内皮细胞在DENV感染中的细胞反应的必要因子。为了解决这一问题，将进行并分析DENV感染的单核细胞/巨噬细胞和血管内皮细胞以及用从感染的单核细胞/巨噬细胞释放的免疫介质处理的血管内皮细胞中的miRNA表达谱。miRNAs在DHF和DSS致病过程中的调控作用将进一步表征。本研究的发现将有助于阐明登革病毒感染中的关键细胞反应，并为DHF免疫发病机制的分子机制提供有价值的见解。这些发现可能会发现新的策略，用于预防和治疗DHF/DSS。