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LncRNA RVRL1 restricts rabies virus infection by disrupting PRC2 complex [ChIP-seq]

ABSTRACT: Rabies is an ancient infectious disease but still lacking efficient therapeutic approach despite of vaccine. In this study, we have identified a novel cytoplasmic lncRNA, namely rabies virus related lncRNA 1(RVRL1), whose expression in neuronal cells is up-regulated upon the infection of the causative agent of rabies, the neurotropic virus rabies virus (RABV). RVRL1 effectively inhibits RABV infection both in neuronal cells and in a mouse model. RVRL1 binds to EZH2 and disrupts the PRC2 complex, which is consistent with the inverse relationship between RVRL1 expression and the cellular H3K27me3 level. RVRL1 expression positively regulates the expression of PCP4L1 encoding a 10 kD peptide, which is shown to inhibit RABV replication. These findings highlight a novel mechanism for lncRNAs to upregulate the expression of antiviral genes, and define two potential anti-rabies reagents including an antiviral lncRNA and an antiviral peptide.

ORGANISM(S): Mus musculus

PROVIDER: GSE107285 | GEO | 2020/09/08

REPOSITORIES: GEO

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LncRNA RVRL1 restricts rabies virus infection by disrupting PRC2 complex [RNA-seq]

Project description:Rabies is an ancient infectious disease but still lacking efficient therapeutic approach despite of vaccine. In this study, we have identified a novel cytoplasmic lncRNA, namely rabies virus related lncRNA 1(RVRL1), whose expression in neuronal cells is up-regulated upon the infection of the causative agent of rabies, the neurotropic virus rabies virus (RABV). RVRL1 effectively inhibits RABV infection both in neuronal cells and in a mouse model. RVRL1 binds to EZH2 and disrupts the PRC2 complex, which is consistent with the inverse relationship between RVRL1 expression and the cellular H3K27me3 level. RVRL1 expression positively regulates the expression of PCP4L1 encoding a 10 kD peptide, which is shown to inhibit RABV replication. These findings highlight a novel mechanism for lncRNAs to upregulate the expression of antiviral genes, and define two potential anti-rabies reagents including an antiviral lncRNA and an antiviral peptide.

2020-09-08 | GSE107277 | GEO

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

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-38975 | biostudies-arrayexpress

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

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

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

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

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2021-12-04 | PXD029404 | Pride

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.

2012-10-10 | GSE26269 | GEO

Genome-wide identification and analysis of gene 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 gene expression level. The hypothesis tested in the present study was that rabies virus (RABV) infection affects the gene expression in brains of mice and RAB with different virulence induce distinct expression pattern in host. Results provide important information that RABV infection led to alteration of gene 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 expression pattern, including immune-related and cellular signaling-related genes.

2012-10-10 | GSE26270 | GEO

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