Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The CCCTC binding factor, CTRL2, controls heterochromatin deposition and the establishment of HSV-1 latency in vivo

ABSTRACT: The cellular insulator CCCTC-binding factor (CTCF) plays a role in HSV-1 latency through the establishment of chromatin boundaries. We previously found that the CTRL2 regulatory element downstream from the LAT enhancer is bound by CTCF during latency and undergoes CTCF eviction at early times post-reactivation in mice latent with 17Syn+ . It has been previously shown that the CTRL2 binding domain is a functional insulator with both enhancer-blocking and silencing capabilities. Considering these findings, we hypothesized that the CTRL2 site plays a key role in regulating latent HSV-1 gene expression. To test this, we used a mutant virus with a 135 bp deletion spanning only the core CTRL2 domain (DCTRL2) in the 17Syn+ background. Following ocular infection of mice, we found significant differences between DCTRL2 and wild-type virus during the acute infection and latency. Notably, mouse mortalities were significantly higher in the DCTRL2 virus compared to the 17Syn+, while lower viral genomes were found after latency indicating that deletion of CTRL2 site disrupted latency establishment. This fact, coupled with increased LAT intron and VP16 expression indicated that the establishment of latency was disrupted in the DCTRL2 mutant. These data provide evidence that chromatin domains of the latent HSV-1 genome are in part maintained by the CTRL2 binding.

ORGANISM(S): Homo sapiens

PROVIDER: GSE128258 | GEO | 2019/04/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

PARP1 Stabilizes CTCF Binding and Chromatin Structure to Maintain Epstein Barr Virus Latency Type

Project description:Epstein Barr Virus (EBV) is a potentially oncogenic gammaherpesvirus that establishes a chronic, latent infection in memory B cells. The EBV genome persists in infected host cells as a chromatinized episome and is subject to chromatin-mediated regulation. Binding of the host insulator protein CTCF to the EBV genome has an established role in maintaining viral latency type. CTCF is post-translationally modified by the host enzyme PARP1. PARP1, or Poly(ADP-ribose) polymerase 1, catalyzes the transfer of a poly(ADP-ribose) (PAR) moiety from NAD+ onto acceptor proteins including itself, histone proteins, and CTCF. PARylation of CTCF by PARP1 can affect CTCF’s insulator activity, DNA binding capacity, and ability to form chromatin loops. Both PARP1 and CTCF have been implicated in the regulation of EBV latency and lytic reactivation. Thus, we predicted that pharmacological inhibition with PARP1 inhibitors would affect EBV latency type through a chromatin-specific mechanism. Here, we show that PARP1 and CTCF colocalize at specific sites throughout the EBV genome, and provide evidence to suggest that PARP1 acts to stabilize CTCF binding and maintain the open chromatin landscape at the active Cp promoter during type III latency. Further, PARP1 activity is important in maintaining latency type-specific viral gene expression. The data presented here provide a rationale for the use of PARP inhibitors in the treatment of EBV-associated cancers exhibiting type III latency, and could ultimately contribute to an EBV-specific treatment strategy for AIDS-related or post-transplant lymphomas.

2018-06-27 | GSE115829 | GEO

The HUSH-SETDB1-MORC2 epigenetic repressor complex restricts herpesvirus infection in association with PML nuclear bodies

Project description:The establishment of latent herpes simplex virus 1 (HSV-1) infection is controlled by promyelocytic leukemia nuclear bodies (PML NBs). Viral genomes are recruited to PML NBs structures and chromatinized by repressive H3.3K9me3 modified H3.3 histone variant to form viral DNA-containing PML-NBs (vDCP NBs). Exactly how this occurs is unclear. Here we identify an essential role for the HUSH complex and its SETDB1 and MORC2 effectors in the establishment and maintenance of latent herpes simplex virus 1 (HSV-1) infection. ChIP-seq analyses conducted on latently/quiescently infected primary human fibroblasts highlight the association of the H3K9me3 mark with the entire viral genome. We demonstrate the necessity of HUSH, SETDB1, and MORC2 in the establishment of repressive heterochromatin in vDCP NBs. Depletion of these components prior to viral infection results in reduced H3K9me3 levels across the entirety of latent/quiescent HSV-1 genomes, with minimal impact on the cellular genome as a whole. Once latency is established, depletion of HUSH, SETDB1, or MORC2 by shRNAs or the HIV-2ROD Vpx protein, induces the reactivation of HSV-1 in infected primary human fibroblasts as well as in human induced pluripotent stem cell-derived sensory neurons (hiPSDN). We discovered that the viral protein ICP0 induces MORC2 degradation via the proteasome machinery. This process is concurrent with ICP0 capability to initiate full HSV-1 reactivation, as well as the significant reactivation of HSV-1 upon MORC2 depletion in hiPSDN. Our data demonstrate the potent antiviral restriction activity of the HUSH/SETDB1/MORC2 complex to a non-integrated human herpesvirus, its close association with PML NBs, and introduces a new target for anti-herpesvirus therapy.

2024-09-24 | GSE263436 | GEO

HSV-1 infection of neural system-derived cells, including SH-SY5Y and U87MG cells at 0, 4 and 10 hour post infection with an MOI of 0.01,to identify the differentially expressed miRNAs and perform pathway enrichment analysis using KEGG.

Project description:we employed human miRNA Microarray assay to identify differentially expressed (DE) miRNAs in response to HSV-1 infection of SH-SY5Y and U87MG cells. The significantly DE miRNAs existed in U87MG but not SH-SY5Y cells at 4 hours post-infection (hpi), HSV-1 latency-associated transcripts (LAT)-derived miRNAs were not abundantly expressed in both SH-SY5Y and U87MG cells, meanwhile, HSV-1 replication was significantly inhibited in U87MG but not SH-SY5Y. Pathway enrichment analysis results showed that target genes of 10 down-regulated DE miRNAs were significantly enriched in Janus kinase-signal transducers and activator of transcription (JAK-STAT) signaling and Herpes simplex virus infection in U87MG cells at 4 hpi. These results indicated that DE of miRNAs may contribute to the HSV-1 replication inhibition in U87MG cells and also may be linked to HSV-1 latency in neurons.

2019-12-03 | GSE141241 | GEO

Human cellular models for Herpes Simplex Virus, type 1 (HSV-1) using induced pluripotent stem cell derived neuronal lineages

Project description:Herpes simplex virus type 1 (HSV-1) is a 152 Kb double stranded DNA alpha-herpesvirus, which establishes long life latent infection in sensory neurons. Most of our knowledge regarding HSV-1 latency comes from in vivo studies using small animal models, mainly rodents and rabbits, which are not naturally infected by HSV-1. Furthermore, these animal models do not fully recapitulate the species specific effects of human HSV-1 infection. Human cellular models utilize trigeminal ganglia removed from cadavers or, alternatively, neuron-like cells derived from cancerous cell lines that do not fully reflect effects on normal human neurons. This limitation poses the need to develop an in vitro model to investigate molecular details of the mechanisms underlying latency and reactivation in human neurons. Induced pluripotent stem (iPS) cell technologies offer an unprecedented opportunity to generate unlimited supplies of neurons and the facility to manipulate such cells in vitro. In this study, we developed an in vitro HSV-1 infection model in human iPS-derived neural progenitor cells (NPCs) and neurons, which displays the main hallmarks of latency defined in animal models and in humans. Induced pluripotent stem (iPS) cells were generated from human skin biopsy samples

2014-05-02 | E-GEOD-46041 | biostudies-arrayexpress

CD4+ T cell transcriptional reprogramming by small compounds

Project description:A major obstacle for HIV eradication is the persistence of latent reservoirs, cells harboring replication competent yet transcriptionally silent proviruses. These reservoirs, composed primarily of CD4+ T cells, cannot be targeted by the host immune system or by combination anti-retroviral therapy (cART). Upon cessation of cART, a rapid viral rebound occurs. In order to develop effective HIV cure therapies, a better understanding of the factors and host programd governing latency establishment and/or maintenance must be obtained. To achieve this goal, we treated a CD4+T cell-based model of latency (J-Lat 10.6) with Latency Reversing Agents (LRAs) and performed bulk RNA-seq to predict host transcriptional programs activated, and potentially involved, in latent HIV reactivation. Our findings suggest that a novel small molecule (EPH-334) reactivates latent HIV by activating an oxidative stress transcriptional program linked to activation of MAPKs and downstream master regulators. Interestingly, the pan histone deacetylase inhibitor SAHA also induces oxidative stress programs potentially linking sensing of redox state aletartions with activation of cell signaling and transcriptioonal programs culminating on latent HIV reactivation.

2020-07-30 | GSE144552 | GEO

Glutamine supplementation suppresses herpes simplex virus reactivation III

Project description:Chronic viral infections are difficult to treat and new approaches, particularly those involving enhancing immune responses are needed. Herpes simplex virus (HSV) establishes latency, reactivates frequently, and breakthrough reactivation can occur despite suppressive antiviral therapy. Virus-specific T cells are important to control HSV, and activated T cells require increased metabolism of glutamine for their proliferation. We found that treatment of HSV-1 latently infected mice and HSV-2 infected guinea pigs with supplemental oral glutamine reduced virus reactivation. Transcriptome analysis of mice treated with glutamine showed that several interferon (IFN)-γ inducible genes were upregulated. Unlike wild-type mice, supplemental glutamine was ineffective in reducing the rate of HSV-1 reactivation in IFN-γ knock-out mice. Mice treated with glutamine had higher numbers of HSV-specific IFN-γ producing CD8 T cells in latently infected ganglia. Thus, glutamine may enhance the IFN-γ-associated immune response and reduce the rate of reactivation of latent virus infection.

2017-08-30 | GSE95715 | GEO

Glutamine supplementation suppresses herpes simplex virus reactivation II

2017-08-30 | GSE95714 | GEO

Glutamine supplementation suppresses herpes simplex virus reactivation I

2017-08-30 | GSE95713 | GEO

Induced pluripotent stem cell derived neuronallineages as human cellular models for Herpes Simplex Virus, type 1 (HSV-1) infections

Project description:Herpes simplex virus type 1 (HSV-1) is a 152 Kb double stranded DNA alpha-herpesvirus, which establishes long life latent infection in sensory neurons. Most of our knowledge regarding HSV-1 latency comes from in vivo studies using small animal models, mainly rodents and rabbits, which are not naturally infected by HSV-1. Furthermore, these animal models do not fully recapitulate the species specific effects of human HSV-1 infection. Human cellular models utilize trigeminal ganglia removed from cadavers or, alternatively, neuron-like cells derived from cancerous cell lines that do not fully reflect effects on normal human neurons. This limitation poses the need to develop an in vitromodel to investigate molecular details of the mechanisms underlying quiescence and reactivation in human neurons. Induced pluripotent stem (iPS) celltechnologies offer an unprecedented opportunity to generate unlimited supplies of neurons and the facility to manipulate such cells in vitro. In this study, we developed an in vitro HSV-1 infection model in human iPS-derived neurons, which displays the main hallmarks of latency defined in animal models and in humans. Our results show for the first time that: i) persistent infection cannot be established in neural progenitor cells (NPCs); ii) the ability of HSV-1 to establish persistent infection is extended to glutamatergic neurons, and not limited to sensory neurons; iii) in neuronal cultures persistently infected with HSV-1, viral genome is localized at the nuclear periphery; iv) HSV-1 acute infection reduces RNA editing at the GluRB site. These results highlight the importance of iPS-based platforms to elucidate unknown aspects of HSV-1 quiescence in human neurons. NPCs were 70-80% confluence

2014-05-02 | E-GEOD-46042 | biostudies-arrayexpress

Single-cell RNA-seq in a model for HIV latency reversal

Project description:T cells are the primary target of the virus HIV-1. Upon infection, the expression of the virus may come to a complete shutdown, a phenomenon known as latency. The molecular mechanisms responsible for the latency of HIV-1 are still poorly understood. To shed light on those mechanisms, we used the J-Lat A2 model for latency reversal, that consists of a Jurkat T cell clone containing a mini HIV construct that is transcriptionally silent. We treated J-Lat A2 and Jurkat cells with the latency-reversing drugs SAHA (suberoylanilide hydroxamic acid) and PMA (phorbol 12-myristate 13-acetate), and we performed single-cell RNA-seq to identify transcriptional signatures shared among the cells where HIV is reactivated.

2021-07-15 | GSE180133 | 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