ScRNASeq of HSV-1 latency
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ABSTRACT:
PROVIDER: PRJEB39022 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:investigated the possible contribution of various cells (i.e., B cells, DCs, fibroblasts, glial cells, ILCs, macrophages, microglia, monocytes, NK cells, neurons, neutrophils, and T cells) isolated from TG of latently infected mice to HSV-1 latency
2023-02-22 | GSE225839 | GEO
Project description: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.
2019-04-05 | GSE128258 | GEO
Project description:HSV-2 coinfection is associated with increased HIV-1 viral loads and expanded tissue reservoirs, but the mechanisms are not well-defined. HSV-2 recurrences result in an influx of activated CD4+ T cells to sites of viral replication and an increase in activated CD4+ T cells in peripheral blood. We hypothesized that HSV-2 induces changes in these cells that facilitate HIV-1 reactivation and replication and tested this hypothesis in human CD4+ T cells and 2D10 cells, a model of HIV-1 latency. HSV-2 promoted latency reversal in HSV-2 infected and bystander 2D10 cells. Bulk and single-cell RNA sequencing studies of activated primary human CD4+ T cells identified decreased expression of HIV-1 restriction factors and increased expression of transcripts including MALAT1 that could drive HIV replication in both the HSV-2-infected and bystander cells. Transfection of 2D10 cells with VP16, an HSV-2 protein that regulates transcription, significantly upregulated MALAT1 expression, decreased trimethylation of lysine 27 on histone H3 protein, and triggered HIV latency reversal. Knockout of MALAT1 from 2D10 cells abrogated the response to VP16 and reduced the response to HSV-2 infection. These results demonstrate that HSV-2 contributes to HIV-1 reactivation through diverse mechanisms including upregulation of MALAT1 to release epigenetic silencing.
2023-05-07 | GSE229391 | GEO
Project description:HSV-2 coinfection is associated with increased HIV-1 viral loads and expanded tissue reservoirs, but the mechanisms are not well-defined. HSV-2 recurrences result in an influx of activated CD4+ T cells to sites of viral replication and an increase in activated CD4+ T cells in peripheral blood. We hypothesized that HSV-2 induces changes in these cells that facilitate HIV-1 reactivation and replication and tested this hypothesis in human CD4+ T cells and 2D10 cells, a model of HIV-1 latency. HSV-2 promoted latency reversal in HSV-2 infected and bystander 2D10 cells. Bulk and single-cell RNA sequencing studies of activated primary human CD4+ T cells identified decreased expression of HIV-1 restriction factors and increased expression of transcripts including MALAT1 that could drive HIV replication in both the HSV-2-infected and bystander cells. Transfection of 2D10 cells with VP16, an HSV-2 protein that regulates transcription, significantly upregulated MALAT1 expression, decreased trimethylation of lysine 27 on histone H3 protein, and triggered HIV latency reversal. Knockout of MALAT1 from 2D10 cells abrogated the response to VP16 and reduced the response to HSV-2 infection. These results demonstrate that HSV-2 contributes to HIV-1 reactivation through diverse mechanisms including upregulation of MALAT1 to release epigenetic silencing.
2023-05-07 | GSE229390 | GEO
Project description:Stacking the odds: multiple sites for HSV-1 latency
| PRJNA937697 | ENA
Project description:Herpes simplex virus type I (HSV-1) establishes a latent infection that evades the host's defense system, and the latent virus can be reactivated by some stimulation. At present,a key problem in the latent studies of HSV-1 has not been clarified, that is, HSV-1 mainly selectively latent in neurons. Therefore, we have found the host transcription factor EGR in Neuro-2a cells by RNA-seq. EGR1 regulates HSV-1 replication and latency by binding to the viral genome or recruiting co-factors. Our data intend to find the role and mechanism of EGR family repressing HSV-1 replication and promoting HSV-1 latency. This study will provide a theoretical basis for the development of drugs to treat of HSV-1 infection.
2025-12-13 | GSE310510 | GEO
Project description:Following acute infection, herpes simplex virus type 1 (HSV-1) establishes life-long latency in neurons. Although sensory neurons in trigeminal ganglia (TG) are primary sites for latency, brainstem is also an important site for latency. For example, the principal sensory nucleus of the spinal trigeminal tract (Pr5) receives afferent inputs from TG and harbors latent HSV-1. The locus coeruleus (LC), is indirectly linked to Pr5. The latency associated transcript (LAT) locus is the only viral gene abundantly expressed during latency, and LAT mediates establishment and maintenance of latency. Previous studies revealed senescent cells inflammation were detected in Pr5 and LC of aged mice and young mice latently infected with HSV-1 indicating HSV-1 influences senescence and inflammation during latency. To expand our understanding of how HSV-1 influences senescence and inflammation in Pr5 and LC, NanoString studies in mice latently infected with wild-type HSV-1 and a LAT-null mutant (dLAT2903) were compared to age matched uninfected C57Bl/6 male and female mice. Cellular genes that regulate neuron differentiation, axonal projection, and pro-inflammatory mediators were more prevalent in mice latently infected with wild-type (wt) HSV-1 and dLAT2903 versus uninfected mice. Thus, HSV-1 latency in Pr5 and LC is not a static process.
2026-06-03 | GSE326523 | GEO
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
Project description:Herpes simplex virus type I (HSV-1) establishes a latent infection that evades the host's defense system, and the latent virus can be reactivated by some stimulation. At present,a key problem in the latent studies of HSV-1 has not been clarified, that is, HSV-1 mainly selectively latent in neurons. Therefore, we have found the host transcription factor EGR in Neuro-2a cells by RNA-seq. EGR1 regulates HSV-1 replication and latency by binding to the viral genome or recruiting co-factors. Our data intend to find the role and mechanism of EGR family repressing HSV-1 replication and promoting HSV-1 latency. This study will provide a theoretical basis for the development of drugs to treat of HSV-1 infection.
2025-12-13 | GSE300560 | GEO
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