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Immune Clearance of Attenuated Rabies Virus Results in Neuronal Survival with Altered Gene Expression

ABSTRACT: Rabies virus (RABV) is a highly neurotropic pathogen that typically leads to mortality of infected animals and humans. The precise etiology of rabies neuropathogenesis is unknown, though it is hypothesized to be due either to neuronal death or dysfunction. Our approach to study the survival and integrity of RABV-infected neurons was to infect Cre reporter mice with recombinant RABV expressing Cre-recombinase (RABV-Cre) to switch neurons constitutively expressing tdTomato (red) to expression of a Cre-inducible EGFP (green), permanently marking neurons that had been infected in vivo. We were able to isolate these previously infected neurons (M-bM-^@M-^\infectedM-bM-^@M-^]) by flow cytometry and assayed their gene expression profiles compared to uninfected cells (M-bM-^@M-^\uninfectedM-bM-^@M-^]) from the same mice. Two cre reporter mice were infected intranasally with RABV-Cre, allowed to resolve the acute infection, and then sacrificed at 3 months post-infection. EGFP+ cells from the brains of these mice were collected by FACS and represent those infected with RABV (M-bM-^@M-^\Infected-1M-bM-^@M-^] and M-bM-^@M-^\Infected-2M-bM-^@M-^]); tdTomato+ cells collected from these same mice represent uninfected cells (M-bM-^@M-^\Uninfected-1M-bM-^@M-^] and M-bM-^@M-^\Uninfected-2M-bM-^@M-^]). RNA was collected from these samples for microarray analysis.

ORGANISM(S): Mus musculus

SUBMITTER: Emily Gomme

PROVIDER: E-GEOD-38975 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Immune Clearance of Attenuated Rabies Virus Results in Neuronal Survival with Altered Gene Expression

Project description:Rabies virus (RABV) is a highly neurotropic pathogen that typically leads to mortality of infected animals and humans. The precise etiology of rabies neuropathogenesis is unknown, though it is hypothesized to be due either to neuronal death or dysfunction. Our approach to study the survival and integrity of RABV-infected neurons was to infect Cre reporter mice with recombinant RABV expressing Cre-recombinase (RABV-Cre) to switch neurons constitutively expressing tdTomato (red) to expression of a Cre-inducible EGFP (green), permanently marking neurons that had been infected in vivo. We were able to isolate these previously infected neurons (M-bM-^@M-^\infectedM-bM-^@M-^]) by flow cytometry and assayed their gene expression profiles compared to uninfected cells (M-bM-^@M-^\uninfectedM-bM-^@M-^]) from the same mice. Two cre reporter mice were infected intranasally with RABV-Cre, allowed to resolve the acute infection, and then sacrificed at 3 months post-infection. EGFP+ cells from the brains of these mice were collected by FACS and represent those infected with RABV (M-bM-^@M-^\Infected-1M-bM-^@M-^] and M-bM-^@M-^\Infected-2M-bM-^@M-^]); tdTomato+ cells collected from these same mice represent uninfected cells (M-bM-^@M-^\Uninfected-1M-bM-^@M-^] and M-bM-^@M-^\Uninfected-2M-bM-^@M-^]). RNA was collected from these samples for microarray analysis.

2012-06-27 | E-GEOD-38970 | biostudies-arrayexpress

Immune Clearance of Attenuated Rabies Virus Results in Neuronal Survival with Altered Gene Expression

2012-06-28 | GSE38975 | GEO

Immune Clearance of Attenuated Rabies Virus Results in Neuronal Survival with Altered Gene Expression

2012-06-28 | GSE38970 | GEO

Transcriptome Analysis of Rabies virus-infected Mice Salivary Glands

Project description:Rabies is a fatal zoonotic disease posing a threat to the public health globally. Rabies virus (RABV) is excreted in the saliva of infected animals, and is primarily transmitted through bite contact. Salivary glands play an important role for virus propagation. However, the significance of salivary glands is less studied in RABV pathogenic mechanisms. To identify functionally important genes in the salivary glands, we employed RNA sequencing (RNA-seq) to establish and analyze mRNA expression profiles in parotid tissue infected with two RABV strains, CVS-11 and PB4. We map the transcriptome changes in response to RABV infection in parotid tissue for the first time. This work provides new clues to the study of RABV-affected salivary gland function and RABV transmission mechanisms in parotid tissue. And the salivary gland-enriched transcripts could be potential targets of interest for rabies disease control.

2023-11-26 | GSE248365 | GEO

Whole transcriptome analysis of FACS purified somatosensory neuron subtypes and whole dorsal root ganglia tissue

Project description:The goal of this study was to analyze global gene expression in specific populations of somatosensory neurons in the periphery, including major, non-overlapping populations that include nociceptors, pruriceptors, and prorioceptors. The mammalian somatosensory nervous system encodes the perception of specific environmental stimuli. The dorsal root ganglion (DRG) contains distinct somatosensory neuron subtypes that innervate diverse peripheral tissues, mediating the detection of thermal, mechanical, proprioceptive, pruriceptive, and nociceptive stimuli. We purified discrete subtypes of mouse DRG somatosensory neurons by flow cytometry using fluorescently labeled mouse lines (SNS-Cre/TdTomato, Parv-Cre/TdTomato) in combination with Isolectin B4-FITC surface staining (IB4). This allowed identification of transcriptional differences between these major populations, revealing enrichment of voltage-gated ion channels, TRP channels, G-protein coupled receptors, transcription factors, and other functionally important classes of genes within specific somatosensory neuron subsets. SNS-Cre mice were bred with Rosa26-TdTomato mice to generate SNS-Cre/TdTomato reporter mice. Parv-Cre mice were bred with Rosa26-TdTomato mice to generate Parv-Cre/TdTomato mice. Isolectin B4-FITC was used to stain the surface of SNS-Cre/TdTomato reporter mice. We used these strategies of fluorescent labeling to purify distinct murine sensory neuron subsets from the dorsal root ganglia (DRG) by fluorescence activated cell sorting (FACS). Neurons were sorted directly in Qiazol for total RNA extraction and microarray analysis. Whole DRG tissue was also included for transcriptome analysis to compare with purified neuronal populations.

2014-12-23 | E-GEOD-55114 | biostudies-arrayexpress

Rabies virus indected Mouse brains LC-MSMS

Project description:Acetylation is the PTM that strongly interlinked with glucose metabolism, so we performed Liquid chromatography–mass spectrometry (LC-MS) to detect acetylated proteins in RABV-infected mouse brains to further investigate the reason how Rabies virus (RABV) infection promotes glucose uptake. To reveal the changes in lysine acetylation due to RABV infection, the brains of mice infected with different RABV strains were harvested for a quantitative proteomic assay.

2021-12-04 | PXD029404 | Pride

mRNA and lncRNA expression profiles between rabies virus infected and untreated human neuroblastoma cells

Project description:Rabies, caused by the rabies virus (RABV), is the oldest known zoonotic infectious disease. Although the molecular mechanisms of RABV pathogenesis have been investigated extensively, the interactions between host and RABV are not clearly understood. It is now known that long non-coding RNAs (lncRNAs) participate in various physiological and pathological processes, but their possible roles in the host response to RABV infection remain to be elucidated. To better understand the pathogenesis of RABV, RNAs from RABV-infected and uninfected human neuroblastoma cells (SK-N-SH) were analyzed using human lncRNA microarrays. We identified 896 lncRNAs and 579 mRNAs that were differentially expressed after infection, indicating a potential role for lncRNAs in the immune response to RABV. Differentially expressed RNAs were examined using Gene Ontology (GO) analysis and were tentatively assigned to biological pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG). A lncRNA-mRNA-transcription factor co-expression network was constructed to relate lncRNAs to regulatory factors and pathways that may be important in virus-host interactions. The network analysis suggests that E2F4, TAF7 and several lncRNAs function as transcriptional regulators in various signaling pathways. This study is the first global analysis of lncRNA and mRNA co-expression during RABV infection, provides deeper insight into the mechanism of RABV pathogenesis, and reveals promising candidate for future investigation.

2019-11-21 | GSE119636 | GEO

Genome-wide identification and analysis of microRNA expression in brains of mice infected with FJDRV, a street rabies virus with high virulence, and ERA, a laboratory-adapted virus with lower virulence

Project description:Host-virus interaction was analyzed at microRNA expression level. The hypothesis tested in the present study was that rabies virus (RABV) infection affects the microRNA expression in brains of mice and RABV with different virulence induce distinct microRNA expression pattern in host. Results provide important information that RABV infection led to alteration of microRNA expression in brains of mice and FJDRV, a street rabies virus with highly virulence isolated from brain of rabid dog in Fujian provice of China, or ERA, a laboratory-adapted rabies virus with lower virulence induced different microRNA expression pattern, and some them may involved in host defense and immune-related function. An nine chip study was performed using total RNA isolated from brains in Treatment 1, three BALB/c mice infected with FJDRV, Treatment 2, three BALB/c mice infected with ERA, and Control, three BALB/c mice non-infected.

2012-10-10 | E-GEOD-26269 | biostudies-arrayexpress

Genome-wide identification and analysis of gene expression in BV-2, a murine microglial cell line, infected with rabies virus CVS-11 (Challenge virus standard)

Project description:The hypothesis tested in the present study was that rabies virus (RABV) infection affects the gene expression in microglial cells. Results provide important information that RABV infection led to alteration of gene expression in microglia. A twelve-chip study was performed using total RNA isolated from RABV- or mock-infected BV-2 at 12, 24, or 48 hpi.

2014-10-10 | E-GEOD-35684 | biostudies-arrayexpress

Genome-wide identification and analysis of microRNA expression in mouse neuroblastoma cells (NA) and BV-2, a murine microglial cell line, infected with rabies virus CVS-11 (Challenge virus standard)

Project description:Rabies virus (RABV) infection led to alteration of microRNA expression in NA and microglia. A sixteen-chip study was performed using total RNA isolated from NA and microglia infected with rabies virus CVS-11 (Challenge virus standard) or mock infected as a control. RNA was isolated from microglia at 12, 24, or 48 hpi and from NA at 24 hpi.

2014-10-10 | E-GEOD-35706 | biostudies-arrayexpress

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