G207 and PVSRIPO treatment of medulloblastoma and pediatric high grade glioma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE233949 | GEO | 2024/01/31
REPOSITORIES: GEO
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Project description:In the course of primary infection with herpes simplex virus 1 (HSV-1), children with inborn errors of the TLR3- and UNC-93B-dependent induction of IFN-α/β and/or IFN-λ immunity are prone to HSV-1 encephalitis (HSE) 1-3. The cells responsible for HSE in these children have yet to be identified. We tested the hypothesis that the pathogenesis of HSE involves non hematopoietic central nervous system (CNS)-resident cells. We derived induced pluripotent stem cells (iPSCs) from the dermal fibroblasts of TLR3- and UNC-93B-deficient patients and from controls. These iPSCs were allowed to differentiate into highly purified populations of neural stem cells (NSCs), neurons, astrocytes and oligodendrocytes. The induction of IFN-β and/or IFN-λ1 in response to poly(I:C) stimulation was dependent on TLR3 and UNC-93B in all cells tested. However, the induction of IFN-β and IFN-λ1 in response to HSV-1 infection was impaired selectively in UNC-93B-deficient neurons and oligodendrocytes. These cells were also much more susceptible to HSV-1 infection than control cells, whereas UNC-93B-deficient NSCs and astrocytes were not. The rescue of UNC-93B-deficient cells with the wild-type UNC93B1 allele demonstrated the genetic defect as the cause of the poly(I:C) and HSV-1 phenotypes. The viral infection phenotype was further rescued by treatment with exogenous IFN-α/β, but not IFN-λ1. TLR3-deficient neurons were also found to be susceptible to HSV-1 infection, a phenotype rescued by wild-type TLR3. Thus, impaired TLR3- and UNC-93B-dependent IFN-α/β intrinsic immunity to HSV-1 in the CNS, in neurons and oligodendrocytes in particular, may underlie the pathogenesis of HSE in children with TLR3 pathway deficiencies One human ESC line (H9) was differentiated into 4 different cell types, neural rosettes, CNS neurons, astrocytes and immature oligodendrocytes. Rosettes were purified manually, neurons were sorted negatively for the surface markers EGFR and CD44, oligodendrocyte cells were positively sorted for the surface marker O4 while astrocytes were enriched by growth in serum containing medium. All cell types were subjected to RNA extraction and hybridization on Illumina microarrays. Each sample has 3 biological repeats, except rosettes which has 2 repeats. In a seperate experiement, undifferentiated H9 cells along with H9-derived neurons and astrocyes as well as UNC93B-/- iPS derived neurons and astrocytes were also subjected to RNA extraction and hybridization on Illumina microarrays.
2012-11-29 | E-GEOD-40593 | biostudies-arrayexpress
Project description:Analysis of transcriptional profiles in whole blood from children < 2 years of age (and healthy matched controls) with RSV, rhinovirus and influenza infection. The hypothesis tested is that transcriptional profile heterogeneity will reflect patient clinical heterogeneity and that RSV infection induces a distinct host response compared with influenza and rhinovirus infection
2013-11-12 | GSE38900 | GEO
Project description:Analysis of transcriptional profiles in whole blood from children < 2 years of age (and healthy matched controls) with RSV, rhinovirus and influenza infection. The hypothesis tested is that transcriptional profile heterogeneity will reflect patient clinical heterogeneity and that RSV infection induces a distinct host response compared with influenza and rhinovirus infection Total RNA extracted from whole blood (lysed in Tempus tubes) drawn from individual pediatric patients with acute RSV, influenza and Rhinovirus lower respiratory tract infection. A total of 241 samples are analyzed: 135 with acute RSV LRTI, 30 with Rhinovirus LRTI, 16 with influenza LRTI, 39 age-sex matched healthy controls and 21 samples obtained one month after the acute hospitalization in children with RSV. Samples GSM1226237-GSM1226272, which were hybridized to Platform GPL10558, were normalized separately from the other Samples in this Series, which were hybridized to Platform GPL6884. 'GSE38900_non-normalized_GSM1226237-GSM1226272.txt.gz' includes the non-normalized data for Samples GSM1226237-GSM1226272; 'GSE38900_non-normalized.txt.gz' includes the non-normalized data for the other Samples.
2013-11-12 | E-GEOD-38900 | biostudies-arrayexpress
Project description:RATIONALE: Human rhinovirus infections cause colds and trigger exacerbations of lower airway diseases. OBJECTIVES: To define changes in gene expression profiles during in vivo rhinovirus infections. METHODS: Nasal epithelial scrapings were obtained before and during experimental rhinovirus infection, and gene expression was evaluated by microarray. Naturally acquired rhinovirus infections, cultured human epithelial cells, and short interfering RNA knockdown were used to further evaluate the role of viperin in rhinovirus infections. MEASUREMENTS AND MAIN RESULTS: Symptom scores and viral titers were measured in subjects inoculated with rhinovirus or sham control, and changes in gene expression were assessed 8 and 48 hours after inoculation. Real-time reverse transcription-polymerase chain reaction for viperin and rhinoviruses was used in naturally acquired infections, and viperin mRNA levels and viral titers were measured in cultured cells. Rhinovirus-induced changes in gene expression were not observed 8 hours after viral infection, but 11,887 gene transcripts were significantly altered in scrapings obtained 2 days postinoculation. Major groups of up-regulated genes included chemokines, signaling molecules, interferon-responsive genes, and antivirals. Viperin expression was further examined and also was increased in naturally acquired rhinovirus infections, as well as in cultured human epithelial cells infected with intact, but not replication-deficient, rhinovirus. Knockdown of viperin with short interfering RNA increased rhinovirus replication in infected epithelial cells. CONCLUSIONS: Rhinovirus infection significantly alters the expression of many genes associated with the immune response, including chemokines and antivirals. The data obtained provide insights into the host response to rhinovirus infection and identify potential novel targets for further evaluation.
2008-05-06 | GSE11348 | GEO
Project description:In the course of primary infection with herpes simplex virus 1 (HSV-1), children with inborn errors of the TLR3- and UNC-93B-dependent induction of IFN-α/β and/or IFN-λ immunity are prone to HSV-1 encephalitis (HSE) 1-3. The cells responsible for HSE in these children have yet to be identified. We tested the hypothesis that the pathogenesis of HSE involves non hematopoietic central nervous system (CNS)-resident cells. We derived induced pluripotent stem cells (iPSCs) from the dermal fibroblasts of TLR3- and UNC-93B-deficient patients and from controls. These iPSCs were allowed to differentiate into highly purified populations of neural stem cells (NSCs), neurons, astrocytes and oligodendrocytes. The induction of IFN-β and/or IFN-λ1 in response to poly(I:C) stimulation was dependent on TLR3 and UNC-93B in all cells tested. However, the induction of IFN-β and IFN-λ1 in response to HSV-1 infection was impaired selectively in UNC-93B-deficient neurons and oligodendrocytes. These cells were also much more susceptible to HSV-1 infection than control cells, whereas UNC-93B-deficient NSCs and astrocytes were not. The rescue of UNC-93B-deficient cells with the wild-type UNC93B1 allele demonstrated the genetic defect as the cause of the poly(I:C) and HSV-1 phenotypes. The viral infection phenotype was further rescued by treatment with exogenous IFN-α/β, but not IFN-λ1. TLR3-deficient neurons were also found to be susceptible to HSV-1 infection, a phenotype rescued by wild-type TLR3. Thus, impaired TLR3- and UNC-93B-dependent IFN-α/β intrinsic immunity to HSV-1 in the CNS, in neurons and oligodendrocytes in particular, may underlie the pathogenesis of HSE in children with TLR3 pathway deficiencies
2012-11-29 | GSE40593 | GEO
Project description:Analysis of transcriptional profiles in whole blood and nasopharyngeal swaps from children hospitalized with lower respiratory tract infections at their admission and their discharge, and diagnosed with either RSV or rhinovirus infections. The hypothesis is that this information will contribute to better understand the viral specific immunity and host responses to RSV infection and may suggest leads for the develoment of vaccines and specific treatment.
2017-04-14 | GSE97742 | GEO
Project description:Analysis of transcriptional profiles in whole blood and nasopharyngeal swaps from children hospitalized with lower respiratory tract infections at their admission and their discharge, and diagnosed with either RSV or rhinovirus infections. The hypothesis is that this information will contribute to better understand the viral specific immunity and host responses to RSV infection and may suggest leads for the develoment of vaccines and specific treatment.
2017-04-14 | GSE97741 | GEO
Project description:Rhinovirus infections exacerbate chronic respiratory inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Airway epithelial cells are the primary site of rhinovirus replication and responsible for initiating the host immune response to infection. Numerous studies have reported that the anti-viral innate immune response in asthma is deficient leading to the conclusion that epithelial innate immunity is a key determinant of disease severity during a rhinovirus induced exacerbation. However, deficient rhinovirus-induced epithelial interferon production in asthma has not always been observed. We hypothesised that disparate in vitro airway epithelial infection models lacking genome-wide, time-course analyses have obscured the role of epithelial innate anti-viral immunity in asthma and COPD. To address this, we developed a low multiplicity of infection (MOI) rhinovirus model of differentiated primary epithelial cells obtained from healthy, asthma and COPD donors. Using genome-wide gene expression following infection, we demonstrated that gene expression patterns are similar across patient groups, but that the kinetics of induction are delayed in cells obtained from asthma and COPD donors. Rhinovirus-induced innate immune responses were defined by interferons (type-I, II and III), interferon response factors (IRF1, IRF3 and IRF7), TLR signalling and NF‐kB and STAT1 activation. Induced gene expression was evident at 24 hours and peaked at 48 hours post‐infection in cells from healthy subjects. In contrast, in cells from donors with asthma or COPD induction was maximal at or beyond 72-96 hours post infection. Thus, we propose that propensity for viral exacerbations of asthma and COPD relate to delayed (rather than deficient) expression of epithelial cell innate anti-viral immune genes which in turns leads to a delayed and ultimately more inflammatory host immune response.
2020-05-10 | GSE146532 | GEO
Project description:We used microarrays to identify genes regulated during oncolytic HSV infection. Oncolytic herpes simplex viruses (oHSV) are promising anticancer therapeutics. We sought to identify alterations in gene expression during oHSV infection of human cancer cells. Human malignant peripheral nerve sheath tumor (MPNST) cells were infected with G207, an ICP34.5-deleted oHSV previously evaluated in clinical trials. G207-infected cells demonstrated massive degradation of cellular mRNAs, while a subset were upregulated. A gene signature of 21 oHSV-induced genes contained 7 genes known to be HSV-induced. Go ontology classification revealed that a majority of upregulated genes are involved in Jak/STAT signaling, transcriptional regulation, nucleic acid metabolism, protein synthesis and apoptosis. Ingenuity-defined functional networks highlighted nodes for AP-1 subunits and interferon signaling via STAT1, SOCS1, SOCS3 and RANTES. Upregulation of SOCS1 correlated with sensitivity of MPNST lines to G207 and depletion of SOCS1 reduced virus replication >1-log. The transcriptome of oHSV-induced genes may predict oncolytic efficacy and provides rationale for next generation oncolytics. Experiment Overall Design: 5 human MPNST cancer cell lines were infected with G207 or mock infected for 6 hours followed by RNA extraction and hybridization on Affymetrix microarrays.
2008-06-16 | E-GEOD-8717 | biostudies-arrayexpress
Project description:The objective of this study was to understand the shared and unique elements of the host transcriptional response to different viral pathogens. We identified 162 subjects in the US and Sri Lanka with infections due to influenza, enterovirus/rhinovirus, human metapneumovirus, dengue virus, cytomegalovirus, Epstein Barr Virus, or adenovirus. Our dataset allowed us to identify common pathways at the molecular level as well as virus-specific differences in the host immune response. Conserved elements of the host response to these viral infections high-lighted the importance of interferon pathway activation. However, the magnitude of the re-sponses varied between pathogens. We also identified virus-specific responses to influenza, enterovirus/rhinovirus, and dengue infections.
2021-10-07 | GSE157240 | GEO