Inhibitors of the histone methyltransferases EZH2/1 induce a potent antiviral state and suppress infection by diverse viral pathogens [array]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE99840 | GEO | 2017/07/17
SECONDARY ACCESSION(S): PRJNA389771
REPOSITORIES: GEO
Similar Datasets
Project description:Epigenetic regulation is based upon a network of complexes that modulate the chromatin character and structure of the genome to impact gene expression, cell fate, and development. Thus, epigenetic modulators represent novel therapeutic targets to treat a range of diseases including malignancies. Infectious pathogens such as herpesviruses are also regulated by cellular epigenetic machinery, and epigenetic therapeutics represent a novel approach to control infection, persistence, and the resulting recurrent disease. The histone methyltransferases EZH2 and EZH1 (EZH2/1) are epigenetic repressors that suppress gene transcription via propagation of repressive H3K27me3 enriched chromatin domains. However, while EZH2/1 are implicated in repression of herpesviral gene expression, inhibitors of these enzymes suppressed HSV primary infection in vitro and in vivo. Furthermore, these compounds blocked lytic viral replication following induction of HSV reactivation in latently infected sensory ganglia. Suppression correlated with the induction of multiple inflammatory, stress, and anti-pathogen pathways as well as enhanced recruitment of immune cells to in vivo infection sites. Importantly, EZH2/1 inhibitors induced a cellular antiviral state that also suppressed infection with DNA (hCMV, Adenovirus) and RNA (Zika virus) viruses. Thus, EZH2/1 inhibitors have considerable potential as general antivirals through activation of cellular antiviral and immune responses.
2017-07-17 | GSE99839 | GEO
Project description:Differentiated NT2 cells are a potentially useful model system to study herpes simples virus (HSV) replication in human neurons. These cells can be irreversibly differentiated into NT-neurons in the presence of retinoic acid and non-dividing cultures NT-neurons can be maintained for up to several months without retinoic acid. HSV is capable of infecting and replicating in differentiated NT-neurons and thus differentiated NT-neurons provide a ready source of human post-mitotic cells which can be useful to study certain aspects of the interaction of HSV and the neuron. Microarray analysis was used to examine how HSV-1 infection modulates cellular transcription in human NT-neurons, focusing on changes that take place during the first 24 hours following infection and compared to changes resulting from infection with inactivated virus. In addition, the transcriptional changes resulting from virus infection of neurons were compared to those observed in primary human fibroblasts. At early times after HSV infection a small number of cellular transcripts in NT-Neurons appear to be increased in abundance. Most of these transcripts that are up-regulated after infection are not unique to neuronal cells, and possibly represent a common cellular response to HSV infection. A few transcripts were not detected in infected human fibroblasts and may represent part of a transcriptional profile specific to this type of human neuronal cell. In contrast to the situation at early times after infection, analysis of cellular transcripts in NT-neurons at late times after infection is complicated by the overall profound decrease in cellular transcription. Thus, microarray analysis appeared to be most useful as a screening method for transcription changes following infection at early times after virus infection of NT-neurons. Two-condition experiment, HSV-1 infected versus uninfected NTNeurons, 4 independent biological replicate sets (uninfected/infected) in dual channel array setup (Cy3/Cy5).
2010-10-15 | E-GEOD-24723 | biostudies-arrayexpress
Project description:Differentiated NT2 cells are a potentially useful model system to study herpes simples virus (HSV) replication in human neurons. These cells can be irreversibly differentiated into NT-neurons in the presence of retinoic acid and non-dividing cultures NT-neurons can be maintained for up to several months without retinoic acid. HSV is capable of infecting and replicating in differentiated NT-neurons and thus differentiated NT-neurons provide a ready source of human post-mitotic cells which can be useful to study certain aspects of the interaction of HSV and the neuron. Microarray analysis was used to examine how HSV-1 infection modulates cellular transcription in human NT-neurons, focusing on changes that take place during the first 24 hours following infection and compared to changes resulting from infection with inactivated virus. In addition, the transcriptional changes resulting from virus infection of neurons were compared to those observed in primary human fibroblasts. At early times after HSV infection a small number of cellular transcripts in NT-Neurons appear to be increased in abundance. Most of these transcripts that are up-regulated after infection are not unique to neuronal cells, and possibly represent a common cellular response to HSV infection. A few transcripts were not detected in infected human fibroblasts and may represent part of a transcriptional profile specific to this type of human neuronal cell. In contrast to the situation at early times after infection, analysis of cellular transcripts in NT-neurons at late times after infection is complicated by the overall profound decrease in cellular transcription. Thus, microarray analysis appeared to be most useful as a screening method for transcription changes following infection at early times after virus infection of NT-neurons. Two-condition experiment, HSV-1 infected versus uninfected NTNeurons, 4 independent biological replicate sets (uninfected/infected) in dual channel array setup (Cy3/Cy5).
2010-10-15 | E-GEOD-24719 | biostudies-arrayexpress
Project description:Differentiated NT2 cells are a potentially useful model system to study herpes simples virus (HSV) replication in human neurons. These cells can be irreversibly differentiated into NT-neurons in the presence of retinoic acid and non-dividing cultures NT-neurons can be maintained for up to several months without retinoic acid. HSV is capable of infecting and replicating in differentiated NT-neurons and thus differentiated NT-neurons provide a ready source of human post-mitotic cells which can be useful to study certain aspects of the interaction of HSV and the neuron. Microarray analysis was used to examine how HSV-1 infection modulates cellular transcription in human NT-neurons, focusing on changes that take place during the first 24 hours following infection and compared to changes resulting from infection with inactivated virus. In addition, the transcriptional changes resulting from virus infection of neurons were compared to those observed in primary human fibroblasts. At early times after HSV infection a small number of cellular transcripts in NT-Neurons appear to be increased in abundance. Most of these transcripts that are up-regulated after infection are not unique to neuronal cells, and possibly represent a common cellular response to HSV infection. A few transcripts were not detected in infected human fibroblasts and may represent part of a transcriptional profile specific to this type of human neuronal cell. In contrast to the situation at early times after infection, analysis of cellular transcripts in NT-neurons at late times after infection is complicated by the overall profound decrease in cellular transcription. Thus, microarray analysis appeared to be most useful as a screening method for transcription changes following infection at early times after virus infection of NT-neurons. Two-condition experiment, HSV-1 infected versus uninfected fibroblasts, 3 independent biological replicate sets (uninfected/infected) in dual channel array setup (Cy3/Cy5).
2010-10-15 | E-GEOD-24724 | biostudies-arrayexpress
Project description:Differentiated NT2 cells are a potentially useful model system to study herpes simples virus (HSV) replication in human neurons. These cells can be irreversibly differentiated into NT-neurons in the presence of retinoic acid and non-dividing cultures NT-neurons can be maintained for up to several months without retinoic acid. HSV is capable of infecting and replicating in differentiated NT-neurons and thus differentiated NT-neurons provide a ready source of human post-mitotic cells which can be useful to study certain aspects of the interaction of HSV and the neuron. Microarray analysis was used to examine how HSV-1 infection modulates cellular transcription in human NT-neurons, focusing on changes that take place during the first 24 hours following infection and compared to changes resulting from infection with inactivated virus. In addition, the transcriptional changes resulting from virus infection of neurons were compared to those observed in primary human fibroblasts. At early times after HSV infection a small number of cellular transcripts in NT-Neurons appear to be increased in abundance. Most of these transcripts that are up-regulated after infection are not unique to neuronal cells, and possibly represent a common cellular response to HSV infection. A few transcripts were not detected in infected human fibroblasts and may represent part of a transcriptional profile specific to this type of human neuronal cell. In contrast to the situation at early times after infection, analysis of cellular transcripts in NT-neurons at late times after infection is complicated by the overall profound decrease in cellular transcription. Thus, microarray analysis appeared to be most useful as a screening method for transcription changes following infection at early times after virus infection of NT-neurons. Two-condition experiment, NTNeurons infected with inactivated HSV-1 versus uninfected NTNeurons, 4 independent biological replicate sets (uninfected/infected) in dual channel array setup (Cy3/Cy5).
2010-10-15 | E-GEOD-24720 | biostudies-arrayexpress
Project description:Differentiated NT2 cells are a potentially useful model system to study herpes simples virus (HSV) replication in human neurons. These cells can be irreversibly differentiated into NT-neurons in the presence of retinoic acid and non-dividing cultures NT-neurons can be maintained for up to several months without retinoic acid. HSV is capable of infecting and replicating in differentiated NT-neurons and thus differentiated NT-neurons provide a ready source of human post-mitotic cells which can be useful to study certain aspects of the interaction of HSV and the neuron. Microarray analysis was used to examine how HSV-1 infection modulates cellular transcription in human NT-neurons, focusing on changes that take place during the first 24 hours following infection and compared to changes resulting from infection with inactivated virus. In addition, the transcriptional changes resulting from virus infection of neurons were compared to those observed in primary human fibroblasts. At early times after HSV infection a small number of cellular transcripts in NT-Neurons appear to be increased in abundance. Most of these transcripts that are up-regulated after infection are not unique to neuronal cells, and possibly represent a common cellular response to HSV infection. A few transcripts were not detected in infected human fibroblasts and may represent part of a transcriptional profile specific to this type of human neuronal cell. In contrast to the situation at early times after infection, analysis of cellular transcripts in NT-neurons at late times after infection is complicated by the overall profound decrease in cellular transcription. Thus, microarray analysis appeared to be most useful as a screening method for transcription changes following infection at early times after virus infection of NT-neurons. Two-condition experiment, HSV-1 infected versus uninfected NTNeurons, 3 independent biological replicate sets (uninfected/infected) in dual channel array setup (Cy3/Cy5).
2010-10-15 | E-GEOD-24722 | biostudies-arrayexpress
Project description:Intrinsic antiviral host factors are proteins that can confer cellular defense by limiting virus replication. Viruses hijack ubiquitin machinery to modify the cellular proteome to subvert these host defenses. The herpes simplex virus 1 (HSV-1) expresses ICP0, which functions as an E3 ubiquitin ligase required to promote infection. Cellular substrates of ICP0 have been discovered as host barriers to infection but the mechanisms for inhibition of viral gene expression are not fully understood. To identify new restriction factors antagonized by ICP0, we compared the proteomes associated with viral DNA (vDNA) during HSV-1 infection with wild-type (WT) virus and a mutant lacking functional ICP0 (ΔICP0). We identified the cellular protein Schlafen 5 (SLFN5) as a new ICP0 target that binds vDNA during HSV-1 ΔICP0 infection. We demonstrated that ICP0 mediates ubiquitination of SLFN5 which leads to its proteasomal degradation. In the absence of ICP0, we demonstrate SLFN5 binds vDNA to represses HSV-1 transcription by limiting accessibility of RNA polymerase II to viral promoters. These results identify SLFN5 as a new restriction factor that inhibits viral transcription and document the first viral countermeasure reported to overcome SLFN antiviral activity.
2020-09-14 | PXD018773 | Pride
Project description:Differentiated NT2 cells are a potentially useful model system to study herpes simples virus (HSV) replication in human neurons. These cells can be irreversibly differentiated into NT-neurons in the presence of retinoic acid and non-dividing cultures NT-neurons can be maintained for up to several months without retinoic acid. HSV is capable of infecting and replicating in differentiated NT-neurons and thus differentiated NT-neurons provide a ready source of human post-mitotic cells which can be useful to study certain aspects of the interaction of HSV and the neuron. Microarray analysis was used to examine how HSV-1 infection modulates cellular transcription in human NT-neurons, focusing on changes that take place during the first 24 hours following infection and compared to changes resulting from infection with inactivated virus. In addition, the transcriptional changes resulting from virus infection of neurons were compared to those observed in primary human fibroblasts. At early times after HSV infection a small number of cellular transcripts in NT-Neurons appear to be increased in abundance. Most of these transcripts that are up-regulated after infection are not unique to neuronal cells, and possibly represent a common cellular response to HSV infection. A few transcripts were not detected in infected human fibroblasts and may represent part of a transcriptional profile specific to this type of human neuronal cell. In contrast to the situation at early times after infection, analysis of cellular transcripts in NT-neurons at late times after infection is complicated by the overall profound decrease in cellular transcription. Thus, microarray analysis appeared to be most useful as a screening method for transcription changes following infection at early times after virus infection of NT-neurons.
2010-10-16 | GSE24719 | GEO
Project description:Differentiated NT2 cells are a potentially useful model system to study herpes simples virus (HSV) replication in human neurons. These cells can be irreversibly differentiated into NT-neurons in the presence of retinoic acid and non-dividing cultures NT-neurons can be maintained for up to several months without retinoic acid. HSV is capable of infecting and replicating in differentiated NT-neurons and thus differentiated NT-neurons provide a ready source of human post-mitotic cells which can be useful to study certain aspects of the interaction of HSV and the neuron. Microarray analysis was used to examine how HSV-1 infection modulates cellular transcription in human NT-neurons, focusing on changes that take place during the first 24 hours following infection and compared to changes resulting from infection with inactivated virus. In addition, the transcriptional changes resulting from virus infection of neurons were compared to those observed in primary human fibroblasts. At early times after HSV infection a small number of cellular transcripts in NT-Neurons appear to be increased in abundance. Most of these transcripts that are up-regulated after infection are not unique to neuronal cells, and possibly represent a common cellular response to HSV infection. A few transcripts were not detected in infected human fibroblasts and may represent part of a transcriptional profile specific to this type of human neuronal cell. In contrast to the situation at early times after infection, analysis of cellular transcripts in NT-neurons at late times after infection is complicated by the overall profound decrease in cellular transcription. Thus, microarray analysis appeared to be most useful as a screening method for transcription changes following infection at early times after virus infection of NT-neurons.
2010-10-16 | GSE24724 | GEO
Project description:Differentiated NT2 cells are a potentially useful model system to study herpes simples virus (HSV) replication in human neurons. These cells can be irreversibly differentiated into NT-neurons in the presence of retinoic acid and non-dividing cultures NT-neurons can be maintained for up to several months without retinoic acid. HSV is capable of infecting and replicating in differentiated NT-neurons and thus differentiated NT-neurons provide a ready source of human post-mitotic cells which can be useful to study certain aspects of the interaction of HSV and the neuron. Microarray analysis was used to examine how HSV-1 infection modulates cellular transcription in human NT-neurons, focusing on changes that take place during the first 24 hours following infection and compared to changes resulting from infection with inactivated virus. In addition, the transcriptional changes resulting from virus infection of neurons were compared to those observed in primary human fibroblasts. At early times after HSV infection a small number of cellular transcripts in NT-Neurons appear to be increased in abundance. Most of these transcripts that are up-regulated after infection are not unique to neuronal cells, and possibly represent a common cellular response to HSV infection. A few transcripts were not detected in infected human fibroblasts and may represent part of a transcriptional profile specific to this type of human neuronal cell. In contrast to the situation at early times after infection, analysis of cellular transcripts in NT-neurons at late times after infection is complicated by the overall profound decrease in cellular transcription. Thus, microarray analysis appeared to be most useful as a screening method for transcription changes following infection at early times after virus infection of NT-neurons.
2010-10-16 | GSE24723 | GEO