Herpes simplex virus type 1 reshapes the host chromatin architecture via transcription machinery hijacking [RNA-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE237079 | GEO | 2025/05/12
REPOSITORIES: GEO
Similar Datasets
Project description:To discover the mechanism by which herpes simplex virus type 1 (HSV-1) widely reshapes the structure of host chromatin during lytic infection, we used chromosome capture technologies (HiC). We infected A549 cells with HSV-1, and analized its chromatin structure before infection and at 1, 3 and 8 hours post infection. We report both Human-Human contacts and Human-Virus trans-contacts.
2025-05-12 | GSE236591 | GEO
Project description:Infection by viruses, including Herpes Simplex virus-1 (HSV-1), and cellular stresses cause widespread disruption of transcription termination (DoTT) of RNA polymerase II (RNAPII). The underlying mechanisms, however, remain unclear. Here we demonstrate that, in HSV-1-infected cells, the viral immediate early factor ICP27 is necessary and sufficient for inducing DoTT. Mechanistically, ICP27 directly binds to the essential mRNA 3’ processing factor CPSF, induces the assembly of a dead-end 3’ processing complex, and blocks mRNA cleavage. Remarkably, ICP27 also acts as a sequence-dependent activator of mRNA 3’ processing for HSV-1 and a subset of host genes. Our results suggest that the bimodal activities of ICP27 play a key role in HSV-1-induced host shutoff and that CPSF is a common host factor targeted by multiple viruses. The mechanism described here may have implications for understanding other virus- and cell stress-mediated regulation of transcription termination.
2019-12-15 | GSE128753 | GEO
Project description:The overall goal of the study was to use in vivo data combined with functional genomics to define gene expression signatures representative of a spectrum of HSV CNS infections. Innate immune deficiencies result in a spectrum of severe clinical outcomes following infection. In particular, there is a strong association between loss of the signal transducer and activator of transcription (Stat) pathway, breach of the blood-brain barrier (BBB), and virus-induced neuropathology. The gene signatures that characterize resistance, disease, and mortality in the virus-infected nervous system have not been defined. Herpes simplex virus type 1 (HSV-1) is commonly associated with encephalitis in humans, and humans and mice lacking Stat1 display increased susceptibility to HSV central nervous system (CNS) infections. In this study, two HSV-1 strains were used, KOS (wild type [WT]), and Δvhs, an avirulent recombinant lacking the virion host shutoff (vhs) function. In addition, two mouse strains were used: strain 129 (control) and a Stat1-deficient (Stat1(-/-)) strain. Using combinations of these virus and mouse strains, we established a model of infection resulting in three different outcomes: viral clearance without neurological disease (Δvhs infection of control mice), neurological disease followed by viral clearance (Δvhs infection of Stat1(-/-) mice and WT infection of control mice), or neurological disease followed by death (WT infection of Stat1(-/-) mice). Through the use of functional genomics on the infected brain stem and liver, we determined gene signatures that were representative of the three infection outcomes. Gender matched, 6- to 8- week old immunocompetent, control 129S6 and 129S6 Stat1 knockout mice were infected corneally with 2x10^6 PFU of either wild type HSV-1, a vhs-null HSV virus, or mock-infected. Brain stems and liver of individual mice were isolated at days 1, 3, 5 and 7 post-inoculation for microarray analysis. For microarray analysis, samples were collected from n=2 animals (1 male, 1 female) per mouse strain and virus strain for each time point. Equal masses of tissue were pooled from two mock-infected mice per time point and run on microarray.
2012-02-21 | E-GEOD-35943 | biostudies-arrayexpress
Project description:Herpes simplex virus 1 (HSV-1) is a widespread human pathogen that establishes lifelong infections, but understanding precise activity at each infection stage remains challenging. HSV-1 utilizes ubiquitination pathways to modulate cellular factors to facilitate its replication cycle, however, elucidating the cascades that follow host protein degradation and the subsequent impact on the host-virus equilibrium continues to be a complex endeavor. Here we reveal the multifaceted role of the DNA damage response protein RAP80 throughout HSV-1’s infection cycle. In early stages, RAP80 inhibits HSV-1 transcription by directly binding to the viral genome, blocking ICP4 (viral protein) binding to transcription factors. This interaction is regulated by phase separation via an intricate interplay between RAP80 and ICP0/ICP4. As infection progresses, the viral E3 ligase ICP0 degrades RAP80, dissolving phase separation, and allowing the formation of a mature viral replication compartment. In late infection stages, RAP80 is deubiquitinated by the viral deubiquitinase UL36USP, which restores cellular homeostasis and promotes HSV-1 survival. This process involves modulating the R-loop-cGAS-apoptosis pathway. These findings underscore the dynamic interplay between viral and host factors and the complex mechanisms used by HSV-1 to subvert host defenses, offering practical implications for the future development of antiviral strategies.
2024-11-13 | GSE281836 | GEO
Project description:The overall goal of the study was to use in vivo data combined with functional genomics to define gene expression signatures representative of a spectrum of HSV CNS infections. Innate immune deficiencies result in a spectrum of severe clinical outcomes following infection. In particular, there is a strong association between loss of the signal transducer and activator of transcription (Stat) pathway, breach of the blood-brain barrier (BBB), and virus-induced neuropathology. The gene signatures that characterize resistance, disease, and mortality in the virus-infected nervous system have not been defined. Herpes simplex virus type 1 (HSV-1) is commonly associated with encephalitis in humans, and humans and mice lacking Stat1 display increased susceptibility to HSV central nervous system (CNS) infections. In this study, two HSV-1 strains were used, KOS (wild type [WT]), and Δvhs, an avirulent recombinant lacking the virion host shutoff (vhs) function. In addition, two mouse strains were used: strain 129 (control) and a Stat1-deficient (Stat1(-/-)) strain. Using combinations of these virus and mouse strains, we established a model of infection resulting in three different outcomes: viral clearance without neurological disease (Δvhs infection of control mice), neurological disease followed by viral clearance (Δvhs infection of Stat1(-/-) mice and WT infection of control mice), or neurological disease followed by death (WT infection of Stat1(-/-) mice). Through the use of functional genomics on the infected brain stem and liver, we determined gene signatures that were representative of the three infection outcomes.
2012-02-21 | GSE35943 | GEO
Project description:Like herpes simplex virus 1 (HSV-1) ICP0 mRNA, HSV-2 ICP0 mRNA is predicted to be targeted by a host neuron-specific microRNA, miR-138. This study was designed to confirm the interaction between HSV-2 ICP0 mRNA and miR-138, and to identify other potential viral and host targets of miR-138 during HSV-2 infection. We performed PAR-CLIP on HSV-2 infected 293T cells overexpressing miR-138 in comparisin to control 293T cells. The results confirmed ICP0 as miR-138's targets, and also identified some other potential viral and host targets of miR-138.
2021-11-01 | GSE155402 | GEO
Project description:Herpes simplex virus type 1 reshapes the host chromatin architecture via transcription machinery hijacking
| PRJNA991604 | ENA
Project description:The goal of this study was to compare the whole transcriptional profile (RNA-seq) of herpes simplex virus type 1 (HSV-1) infected and mock infected human fibroblast KMB17 strain at 48 hours post infection.There is increasing evidence that circular RNAs (circRNAs) are involved in diverse pathogenesis processes; however, their roles in virus infection remain unclear. Here, we profiled global changes of circRNAs, genes and microRNA (miRNAs) under herpes simplex virus type 1 (HSV-1) infection by RNA-seq. Numerous dysregulated transcripts comprised of 536 circRNAs, 3,885 genes and 207 miRNAs were found during viral infection. The dysregulated genes were enriched to NOD-like receptor signaling pathway, Jak-STAT signaling pathway and pathways of apoptosis, cell cycle progression and cell death, all of which may be implicated in viral pathogenesis and cellular immunity. Further integration analysis of circRNAs, genes and miRNAs reveals putative involvement of circRNAs in viral pathogenesis and antiviral immunity by circRNA-miRNA-gene regulatory axis. This work provides a comprehensive view for dysregulated circRNAs induced by HSV-1 and their interplay with miRNAs and genes, thus offering new insights into the mechanisms of interactions between HSV-1 and its host.
2017-09-13 | GSE103763 | GEO
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
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 | GSE95714 | GEO