Herpes simplex encephalitis in a patient with a new form of inherited IFNAR1 deficiency
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA663472 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12641828_1.fastq.gz | Fastqsanger.gz | |||
| SRR12641828_2.fastq.gz | Fastqsanger.gz | |||
| SRR12641829_1.fastq.gz | Fastqsanger.gz | |||
| SRR12641829_2.fastq.gz | Fastqsanger.gz | |||
| SRR12641830_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 120 |
Similar Datasets
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
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
Project description:Inborn errors of TLR3-dependent IFN-α/β- and IFN-λ-mediated immunity in the CNS can underlie herpes simplex virus 1 (HSV-1) encephalitis (HSE). The respective contributions of IFN-α/β and IFN-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 of HSE at the age of 2 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, less severe, 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 genome-wide induction of IFN-stimulated genes. The patient's 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 viral disease occurred in natural conditions, unlike those previously reported in other patients with IFNAR1 or IFNAR2 deficiency. This experiment of nature indicates that IFN-α/β are essential for anti-HSV-1 immunity in the CNS.
| S-EPMC7773360 | biostudies-literature
Project description:We hypothesize that human RIPK3 deficiency does not result in impairment of type I IFN mediated antiviral immunity, contrasting with the situation in deficiencies of the TLR3-IFNAR1 circuit. To test the cellular responses to HSV1 at the wide transcriptome level, bulk RNA sequencing was performed with human primary fibroblasts without or with HSV-1 infection for 24 hours, in cells from healthy controls, RIPK3 HSE patient and other patients with recessive TLR3, IFNAR1 or NEMO deficiency.
2023-03-29 | GSE228495 | GEO
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
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
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
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
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
Project description:Herpes simplex virus mutants lacking the vhs gene are severely attenuated in animal models of pathogenesis and exhibit reduced growth in primary cell culture. As a result of these properties vhs-deleted virus have been proposed as live-attenuated viruses. Despite these findings and their implications for vacccines, the mechanisms by which vhs promotes infection in cell culture and in vivo are not understood. In this study we demonstrate that vhs-deficent viruses replicate to reduced levels in interferon(IFN)- primed cells. Furthermore, vhs-defective viruses induce increased levels of IFN? and IFN?-stimulated genes, and increased levels of eIF2? phosphorylation in infected cells. In addition, we demonstrate a generalized over-expression of viral RNAs following infection with a vhs-deficient virus. This suggests increased expression of IFN pathway inducing double stranded RNA, a potent pathogen-associated molecular pattern (PAMP). Together these data show that vhs likely functions to reduce innate immune responses and thereby acts as critical determinant of viral pathogenesis. Keywords: time course, genetic modification Time course (1,3,6,9 & 12h) of HSV infected mouse embryo fibroblasts. Wild type (KOS) virus is co-hybridized with vhs null virus (NHB). Each time-point is hybridized in quadruplicate.
2008-04-03 | E-GEOD-10962 | biostudies-arrayexpress