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Intranasal therapy with miRNA-219 reduces viral load and encephalomyelitis in the TMEV model of multiple sclerosis

ABSTRACT: Intranasal therapy with miRNA-219 reduces viral load and encephalomyelitis in the TMEV model of multiple sclerosis

PROVIDER: PRJNA418974 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6305150.fastq.gz	Fastqsanger.gz
	SRR6305160.fastq.gz	Fastqsanger.gz
	SRR6305170.fastq.gz	Fastqsanger.gz
	SRR6305180.fastq.gz	Fastqsanger.gz
	SRR6305151.fastq.gz	Fastqsanger.gz

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Intranasal therapy with miRNA-219 reduces viral load and encephalomyelitis in the TMEV model of multiple sclerosis

Project description:Purpose: RNA sequencing of spinal cord following intranasal administration of miRNA-219 in Theiler’s murine encephalomyelitis virus (TMEV) model of multiple sclerosis Methods: RNA isolated from spinal cords was analyzed by Next-Generation RNA Sequencing (Illumina) Results: Here, we analyzed the therapeutic effects of miR-219 in a virus-induced demyelinating model. Following intranasal administration of miR-219 in TMEV-infected mice, we found significant reduction of clinical signs, virus persistence (virus genome copy numbers), neuroglia activation, proinflammatory cytokine levels, and demyelination. RNA sequencing of expressed host genes demonstrated that miR-219 potentiates transcriptional changes in cholesterol-related genes, leading to reduced levels of this lipid. Conclusions: Since virus replication relies on hijacking cholesterol biosynthesis and trafficking of host cell endogenous pools as well as remodeling intracellular membranes, i.e., the virus replication organelles or viroplasm, treatment with miR-219 may interfere with virus RNA replication through downregulation of cholesterol synthesis. Our findings show that miR-219 administration lessens pathological changes by reducing the CNS virus loads and favoring myelin repair.

2020-11-16 | GSE107091 | GEO

Klebsiella pneumoniae strain:219-96 | isolate:219-96

Project description:Klebsiella pneumoniae strain:219-96 | isolate:219-96 Genome sequencing

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Mock, latent, and lytic rKSHV.219-infected iSLK cells [Expt3]

Project description:Expression profiling of stably infected epithelial cells using a custom tiling microarray. iSLK was infected with rKSHV.219 and selected with puromycin. Mock infected iSLK served as control for iSLK.219. Lytic reactivation of iSLK.219 was induced with 1 ug/mL doxycycline for 48 hours.

2013-03-29 | GSE45599 | GEO

Sinorhizobium meliloti strain:219

Project description:Sinorhizobium meliloti 219 Resequencing

| PRJNA501497 | ENA

Bradyrhizobium japonicum strain:USDA 219 | isolate:USDA 219

Project description:Bradyrhizobium japonicum USDA 219 genome sequencing

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microRNA-219 Reduces Viral Load and Pathologic Changes in Theiler's Virus-Induced Demyelinating Disease.

Project description:Analysis of microRNA (miR) expression in the central nervous system white matter of SJL mice infected with the BeAn strain of Theiler's murine encephalomyelitis virus (TMEV) revealed a significant reduction of miR-219, a critical regulator of myelin assembly and repair. Restoration of miR-219 expression by intranasal administration of a synthetic miR-219 mimic before disease onset ameliorates clinical disease, reduces neurogliosis, and partially recovers motor and sensorimotor function by negatively regulating proinflammatory cytokines and virus RNA replication. Moreover, RNA sequencing of host lesions showed that miR-219 significantly downregulated two genes essential for the biosynthetic cholesterol pathway, Cyp51 (lanosterol 14-?-demethylase) and Srebf1 (sterol regulatory element-binding protein-1), and reduced cholesterol biosynthesis in infected mice and rat CG-4 glial precursor cells in culture. The change in cholesterol biosynthesis had both anti-inflammatory and anti-viral effects. Because RNA viruses hijack endoplasmic reticulum double-layered membranes to provide a platform for RNA virus replication and are dependent on endogenous pools of cholesterol, miR-219 interference with cholesterol biosynthesis interfered virus RNA replication. These findings demonstrate that miR-219 inhibits TMEV-induced demyelinating disease through its anti-inflammatory and anti-viral properties.

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miR-219 Cooperates with miR-338 in Myelination and Promotes Myelin Repair in the CNS

Project description:microRNAs (miRNAs) have been implicated in oligodendrogenesis and demyelinating diseases; however, identification of individual miRNAs responsible has remained elusive. Through targeted mutagenesis, we find that miR-219 is required for proper oligodendrocyte differentiation and myelination in vivo. Deletion of miR-338 together with miR-219 further exacerbates hypomyelination phenotypes. Temporally specific ablation reveals a critical role for miR-219 in oligodendrocyte remyelination after demyelination, while overexpression of miR-219 promotes precocious oligodendrocyte maturation and myelin regeneration. Accordingly, administration of miR-219 mimics to lysolecithin-induced demyelinating lesions in the murine spinal cord and brain enhances myelin restoration. Through integrating analyses of transcriptome profiling and biotin-affinity miRNA pull-down, we identify a set of stage-specific targets of miR-219, including Etv5 and Lingo1, as oligodendrocyte differentiation inhibitors. Inhibiting Etv5 and Lingo1 leads to a partial rescue of differentiation defects observed in miR-219-mutant OLs in vitro. Together, our findings identify context-specific miRNA-regulated checkpoints that control CNS myelinogenesis and myelin repair.

2017-04-21 | GSE80439 | GEO

Paenibacillus elgii strain:219

Project description:Paenibacillus elgii strain:219 Genome sequencing

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Panicum virgatum cultivar:SPR-219

Project description:Panicum virgatum exome capture - SPR-219

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Quantitative proteomic analysis of experimental autoimmune encephalomyelitis mice implicates SUMOylation in multiple sclerosis

Project description:In this study, we performed quantitative proteomics utilizing a data-independent acquisition (DIA) strategy to investigate the proteome alteration in the brain and spinal cord tissues from mice with experimental autoimmune encephalomyelitis (EAE), a widely-used model for MS.

2024-03-20 | PXD050789 |

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