Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The c-Rel transcription factor limits early interferon and neuroinflammatory responses to prevent herpes simplex encephalitis onset in mice

ABSTRACT: The c-Rel transcription factor limits early interferon and neuroinflammatory responses to prevent herpes simplex encephalitis onset in mice

PROVIDER: PRJNA714059 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR13952652_1.fastq.gz	Fastqsanger.gz
	SRR13952652_2.fastq.gz	Fastqsanger.gz
	SRR13952653_1.fastq.gz	Fastqsanger.gz
	SRR13952653_2.fastq.gz	Fastqsanger.gz
	SRR13952654_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 38

Similar Datasets

The c-Rel transcription factor limits early interferon and neuroinflammatory responses to prevent herpes simplex encephalitis onset in mice

Project description:c-Rel is a transcription factor and a subunit of NF-kΒ encoded by the Rel gene. We previously demonstrated that a truncating cysteine to stop codon mutation at amino acid position 307 of c-Rel (RelC307X) results in susceptibility to herpes simplex virus type 1 (HSV-1). Approximately 60% of mutant RelC307X mice succumb to lethal herpes simplex encephalitis (HSE) in the hindbrain between days 6 and 9 postinfection, compared to resistant wild-type (Rel+/+) controls. Here, we performed dual host-pathogen RNA sequencing on Rel+/+ and RelC307X brainstems to measure differential viral and host gene expression that may underlie HSE susceptibility in mutant mice. Briefly, brainstems were harvested from Rel+/+ and RelC307X mice prior to HSE symptom onset at day 5 post-HSV-1 infection, compared to brainstems collected from non-infected control mice. Total RNA was isolated from bulk tissue using TRIzol (Invitrogen) and further column-purified using the RNeasy Mini Kit (Qiagen). RNA quality was assessed using Bioanalyzer RNA Pico chips (Agilent), and libraries were prepared following rRNA depletion. Libraries were sequenced on an Illumina HiSeq 2500 sequencer in paired-end 50bp configuration. Sequencing reads were aligned to both mouse and HSV-1 strain 17 reference genomes to obtain both host and viral gene expression counts. In total, 5 Rel+/+ and 6 RelC307X brainstem samples were analyzed at day 5 post-infection, and 4 Rel+/+ and 4 RelC307X independent non-infected samples as controls. Day 5 HSV-1-infected samples were further subdivided into high- or low-responder within both genotype groups based in part on the level of viral and host defence gene expression in each sample.

2021-10-29 | GSE168799 | GEO

Host miRNA molecular signatures in the brains of mice are associated with acute herpes simplex virus 1 encephalitis

Project description:Transcriptional profiling of mouse brain regions (microdissection of cerebellum and hippocampus regions) comparing control, untreated brain tissue with HSV-1 infected brain tissue. Two viral tires, 10^3 and 10^6 plaque forming units of HSV-1 strain F, were intracerebrally inoculated into the brain of SJL/J strain of mice. The goal was to assess global transcriptional dynamics in HSV-1 infected mice, a model of herpes simplex encephalitis, as compared to controls (either PBS or Vero cell suspension). The microarray data identified fluctuations in gene expression where many of these genes were also potential targets of miRNA-200 and miR-183 family members which were themselves upregulated within the same brain samples.

2016-11-01 | GSE51040 | GEO

Herpes simplex virus infections of cortical brain cells: the proteome and secretome of the host

Project description:Herpes simplex virus-1 (HSV-1) infections of the brain cause a severe neuroinflammatory condition – Herpes simplex encephalitis (HSE). During the acute phase, HSV-1 changes the host cells to facilitate its own replication and to escape host immunity. However, the host reacts with a severe neuroinflammation which may be beneficial for viral clearance or detrimental inducing neuronal damage and hindering regeneration. Indeed, surviving HSE-patients often suffer from an incomplete regeneration with memory deficits and other neuropsychiatric symptoms. HSV-1 infects different cell types such as neurons, astrocytes, and oligodendrocytes all of which participate in the host response. This includes a changed paracrine signaling. However, the host response has not been characterized on a global molecular level so far. Here, we infected primary mixed cortical cells with HSV-1 and analyzed the proteome and the secretome of the host. We identified 28 differentially regulated proteins in the host proteome involved in endocytosis, vesicle trafficking at the golgi-apparatus, and inflammasome formation. In the secretome, we identified 71 differentially regulated proteins with a subset involved in axonal regeneration. Endocytosis and vesicle trafficking are critical for viral entry and envelopment. The suppression of inflammasome activity is crucial for viral spread. Thus, our proteomic analysis hints for potential molecules regulating viral production and spread in brain cells. Moreover, the secretome analysis gives rise to a set of proteins involved in neuroregeneration.

2021-09-09 | PXD018819 | Pride

TMEFF1 is a neuron-specific restriction factor for herpes simplex virus

Project description:The brain is highly sensitive to damage caused by infection and inflammation. Herpes simplex virus-1 (HSV-1) is a neurotropic virus and the cause of herpes simplex encephalitis. It is unknown whether neuron-specific antiviral factors control virus replication to prevent infection and excessive inflammatory responses, hence protecting the brain. Using genome-wide CRISPR screening for HSV-1 restriction factors, we identified TMEFF1, which is expressed specifically in CNS neurons and not regulated by type I interferon, as the best-known innate antiviral system controlling virus infections. Depletion of TMEFF1 in stem-cell-derived human neurons led to elevated viral replication and neuronal death upon HSV-1 infection. TMEFF1 blocked the HSV-1 replication cycle at the level of viral entry through interactions with Nectin-1 and non-muscle myosin heavy chain IIA/B, which are core proteins in virus-cell binding and virus-cell fusion, respectively. Importantly, Tmeff1-/- mice exhibited increased susceptibility to HSV-1 infection in the brain but not in the periphery. Within the brain, elevated viral load was observed specifically in neurons. Our study identifies TMEFF1 as a neuron-specific restriction factor essential for prevention of HSV-1 replication in the CNS.

2024-07-24 | GSE268182 | GEO

Herpes simplex encephalitis in a patient with a new form of inherited IFNAR1 deficiency

Project description:Inborn errors of TLR3-dependent IFN-α/β- and -λ-mediated immunity in the central nervous system (CNS) can underlie herpes simplex virus 1 (HSV-1) encephalitis (HSE). The respective contributions of IFN-α/β- and -λ are unknown. We report a child homozygous for a genomic deletion of the entire coding sequence and part of the 3’UTR of the last exon of IFNAR1, who died from HSE at the age of two years. An older cousin died following vaccination against measles, mumps and rubella at 12 months of age, and another 17-year-old cousin homozygous for the same variant has had other viral illnesses. The encoded IFNAR1 protein is expressed on the cell surface but is truncated and cannot interact with the tyrosine kinase TYK2. The patient’s fibroblasts and EBV-B cells did not respond to IFN-α2b or IFN-β, in terms of STAT1, STAT2 and STAT3 phosphorylation, or the induction of IFN-stimulated genes (ISGs). Transcriptome analysis revealed a complete abolition of genome-wide ISG induction in response to IFN-α2b in IFNAR1-deficient fibroblasts from the patient. These fibroblasts were susceptible to viruses, including HSV-1, even in the presence of exogenous IFN-α2b or IFN-β. HSE is therefore a consequence of inherited complete IFNAR1 deficiency. This experiment of Nature indicates that IFN-α/β are essential for anti-HSV-1 immunity in the CNS.

2020-09-24 | GSE157948 | GEO

Herpes simplex encephalitis in a patient with a new form of inherited IFNAR1 deficiency

Project description:Herpes simplex encephalitis in a patient with a new form of inherited IFNAR1 deficiency

| PRJNA663472 | ENA

Widespread activation of antisense transcription of the host genome during Herpes simplex virus 1 infection

Project description:We show that Herpes simplex virus 1 (HSV-1) induces the expression of about 1000 antisense transcripts from the human host cell genome.

2017-09-28 | GSE97009 | GEO

The c-Rel transcription factor limits early interferon and neuroinflammatory responses to prevent herpes simplex encephalitis onset in mice.

Project description:Herpes simplex virus type 1 (HSV-1) is the predominant cause of herpes simplex encephalitis (HSE), a condition characterized by acute inflammation and viral replication in the brain. Host genetics contribute to HSE onset, including monogenic defects in type I interferon signaling in cases of childhood HSE. Mouse models suggest a further contribution of immune cell-mediated inflammation to HSE pathogenesis. We have previously described a truncating mutation in the c-Rel transcription factor (RelC307X) that drives lethal HSE in 60% of HSV-1-infected RelC307X mice. In this study, we combined dual host-virus RNA sequencing with flow cytometry to explore cell populations and mechanisms involved in RelC307X-driven HSE. At day 5 postinfection, prior to HSE clinical symptom onset, elevated HSV-1 transcription was detected together with augmented host interferon-stimulated and inflammatory gene expression in the brainstems of high-responding RelC307X mice, predictive of HSE development. This early induction of host gene expression preceded pathological infiltration of myeloid and T cells in RelC307X mice at HSE onset by day 7. Thus, we establish c-Rel as an early regulator of viral and host responses during mouse HSE. These data further highlight the importance of achieving a balanced immune response and avoiding excess interferon-driven inflammation to promote HSE resistance.

| S-EPMC8551191 | biostudies-literature

Histone deacetylase inhibitors (HDACi) enhance oncolytic herpes simplex virus in malignant meningioma.

Project description:The goal of the study was to determine whether low dose HDACi sensitizes human malignant meningioma cells to the cytotoxic capacity of oncolytic herpes simplex virus G47delta. RNA sequencing was used to examine transcriptomic changes mediated by HDACi preexposure before oncolytic virus infection.

2022-08-02 | GSE210178 | GEO

RNA-seq identification of herpes simplex virus type 1 transcription in Neuro-2a cells overexpressing ONECUT2

Project description:This is a part of the study that shows that a host gene,ONECUT2 (OC2), promote herpes simplex virus 1 (HSV-1) transcription. These RNA-seq analyses viral genes transcription in Neuro-2a cells. Neuro-2a cells were transfected with pOC2△HOX2 and pcDNA plasmids for 42 hours then infected with herpes simple virus1 for 5 hours.

2023-09-18 | GSE241029 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data