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

Role of Exosomes in the Crosstalk Between Brain Endothelium and HIV Neuroinvasion

外泌体在脑内皮细胞和 HIV 神经侵袭之间串扰中的作用

基本信息

批准号：
9203185
负责人：
Jieliang Li
金额：
$ 23.4万
依托单位：
TEMPLE UNIV OF THE COMMONWEALTH
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-20 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9203185
关键词：
Address Antiviral Agents Astrocytes Biomedical Engineering Blood - brain barrier anatomy Brain Cell Culture Techniques Cell Line Cells Cerebrospinal Fluid Data Databases Destinations Endothelial Cells Endothelium Event Family Gene Expression HIV HIV Infections Hemostatic function Immune Immunologic Surveillance In Vitro Inflammation Injury Interferon-beta Interferons Mediating Mediator of activation protein MicroRNAs Natural Immunity Neoplasm Metastasis Nerve Degeneration Neuraxis Neurons Neuropathogenesis Organ Permeability Pilot Projects Plasma Play Primary Infection Process Proteins Refractory Reporting Research Role Scheme Side Small RNA TLR3 gene Tight Junctions Validation Viral Virus Virus Diseases brain cell brain endothelial cell brain parenchyma cerebral capillary differential expression exosome extracellular vesicles foot in vivo insight intercellular communication macrophage migration monocyte neurocognitive disorder neuronal survival neurotoxic neurotoxicity neurovascular novel pathogen prediction algorithm protein expression transcriptome sequencing tumor

项目摘要

Summary Exosomes are emerging to play an important role in immune surveillance and neuronal survival of the central nervous system (CNS), as they mediate the intercellular communications between neurons and other brain cells, including astrocytes and neurovascular endothelial cells. However, the role of exosomes in HIV-mediated neuroinvasion is largely unknown. We recently identified that exosomes isolated from the plasma of HIV-infected subjects contain significantly high levels of microRNA-17 (miR- 17) and miR-20a that can target tight junction proteins ZO-1 and JAM-2. A further pilot study using cell culture-derived exosomes showed that exosomes from HIV-infected macrophages breached blood-brain barrier (BBB) integrity. Thus, we hypothesize that exosomes derived from plasma of HIV-infected subjects contain miRNAs that impair BBB functions, facilitating organotropic viral dissemination to the brain and resulting in neurodegeneration. We propose two specific aims to address this hypothesis: Aim 1. To investigate the effect of plasma exosomes from HIV-infected subjects or uninfected controls on BBB functions and identify the role of miR-17 and miR-20a in this process. Aim 2. To profile and compare the miRNA spectra of exosomes from the plasma and cerebrospinal fluid of HIV- infected subjects with or without neurocognitive disorders. The functional significance of the exosomes and the differentially expressed exosomal miRNAs will be validated on neuronal survival, astroglial differentiation and BBB functions. This project, with both in vitro and in vivo studies, should provide novel pathogenetic insights into HIV infection of the CNS.

总结