Genome-wide map of viral transcription factor ORF34 binding in Kaposi's Sarcoma Herpesvirus (KSHV)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA522742 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8582190.fastq.gz | Fastqsanger.gz | |||
| SRR8582191.fastq.gz | Fastqsanger.gz | |||
| SRR8582192.fastq.gz | Fastqsanger.gz | |||
| SRR8582193.fastq.gz | Fastqsanger.gz | |||
| SRR8582194.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:Kaposi's sarcoma (KS) may derive from Kaposi's Sarcoma Herpesvirus (KSHV)-infected human Mesenchymal Stem Cells (hMSCs) that migrate to sites characterized by inflammation and angiogenesis, promoting the initiation of KS. By analyzing the RNA sequences of KSHV-infected primary hMSCs, we have identified specific cell subpopulations, mechanisms, and conditions involved in the initial stages of KSHV-induced transformation and reprogramming of hMSCs into KS progenitor cells. Under pro-angiogenic environmental conditions, KSHV can reprogram hMSCs to exhibit gene expression profiles more similar to KS tumors, activating cell cycle progression, cytokine signaling pathways, and endothelial differentiation indicating the involvement of KSHV infection in inducing the Mesenchymal-to-Endothelial (MEndT) transition of hMSCs. This finding underscores the significance of this condition in facilitating KSHV-induced proliferation and reprogramming of hMSCs towards MEndT and closer to KS gene expression profiles, providing further evidence of these cell subpopulations as precursors of KS cells that thrive in a pro-angiogenic environment.
2024-07-08 | GSE260925 | GEO
Project description:The integrator complex (INT) is an essential regulator of RNA biogenesis across evolution. Most current findings describe INT's function in states of equilibrium, presenting a research gap in INT's role in dynamic states, such as in infections and cancers. Viruses hijack cellular RNA machinery to transcribe their genes and produce viral progeny, presenting a unique condition to investigate INT-dependent RNA regulation under perturbation. Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic DNA virus that causes two deadly cancers, Kaposi's sarcoma and primary effusion lymphoma. KSHV undergoes a highly regulated and robust transcription of viral genes upon lytic reactivation, providing a complex and dynamic system to investigate integrator-mediated viral/host RNA regulation. We find that integrator subunit 11 (INTS11), the enzymatic core of INT, is essential for KSHV lytic replication triggered by reactivation or primary infection. Further RNA-seq analyses revealed a dynamic and unique signature of human transcriptomes during each lytic stage, respectively. Although the knockdown of INTS11 resulted in selective upregulation and downregulation of certain human gene transcription, INTS11's loss globally repressed the KSHV transcriptome throughout KSHV lytic replication. This inhibited viral lytic gene expression, viral genome replication, and virion production. Integrator subunits 9 and 6 are also important for KSHV lytic replication. Mechanistically, ChIP-seq analysis showed that INTS11 is increasingly recruited to the KSHV genome with some unique binding patterns as the lytic cycle progresses, suggesting that KSHV hijacks INTS11 during lytic gene transcriptions. In all, our findings reveal the essential roles of the Integrator complex in KSHV lytic replication.IMPORTANCEThe integrator complex (INT) is essential for RNA metabolism and is fundamental to all organisms, but its function and regulation during viral infection are not well described. Kaposi's sarcoma-associated herpesvirus (KSHV) infection establishes lifelong infection and causes two deadly cancers; however, no vaccine is available. Using KSHV as a model, we found that integrator subunit 11 (INTS11), the enzymatic core of INT, is recruited to the KSHV genome under lytic phases and plays an essential role in facilitating global KSHV lytic mRNA transcription and viral production. This reveals the critical role of INT in viral infection, a common and inevitable event in human life.
2025-06-25 | GSE300543 | GEO
Project description:Transfection of a Kaposi's sarcoma (KS) herpesvirus (KSHV) Bacterial Artificial Chromosome (KSHVBac36) into mouse bone marrow endothelial lineage cells generated a cell (mECK36) that induced KS-like tumors in mice. mECK36 formed KSHV-harboring vascularized spindle-cell sarcomas that were LANA+ and displayed a KSHV and host transcriptomes reminiscent of KS tumors. Keywords: Cell type comparison
2007-01-01 | GSE6482 | GEO
Project description:RNA sequencing analysis to identify gene targets of Kaposi's sarcoma herpesvirus (KSHV) ORF24
| PRJNA522743 | ENA
Project description:Deregulation of host lncRNAs following infection with Kaposi’s sarcoma-associated herpesvirus (KSHV) was assessed. Total RNA was prepared from uninfected TIVE cells (telomerase-immortalized vein endothelial cells), and from TIVE cells latently infected with either wild-type KSHV or with a deletion mutant (Δcluster-KSHV) lacking ten of the twelve KSHV microRNA genes. The RNA was converted to labeled cRNA and used to probe a human lncRNA microarray. The goal was to investigate which host lncRNAs were either up- or down-regulated during latent infection with KSHV, and to determine if deregulation of host lncRNAs was dependent on KSHV miRNAs.
2017-07-12 | GSE89114 | GEO
Project description:The aging process is characterized by cellular functional decline and increased susceptibility to infections. Understanding the association between virus infection and aging is crucial for developing effective strategies against viral infections in older individuals. Kaposi's sarcoma-associated herpesvirus (KSHV) infection increases the risk of Kaposi's sarcoma, a vascular cancer prevalent among the elderly without HIV infection. However, the relationship between KSHV pathogenesis and cellular senescence remains unknown. Here, we demonstrate that KSHV infectivity is significantly increased in senescent human endothelial cells due to enhanced binding of virions to cell surface. Proteomic analysis identified caveolin-1 and CD109 that promote KSHV infection and were significantly upregulated in senescent cells. In particular, CD109 is expressed on cell surface and directly interacts with KSHV virions to enhance KSHV infection. Knockout of CD109 abolished while overexpression of CD109 promote KSHV binding to cell surface, and infectivity. These results identify CD109 as a novel KSHV entry receptor that enhances KSHV infection in senescent cells, which might in part explain the higher sensitivity of elder subjects to KSHV infection and Kaposi's sarcoma.
2024-04-17 | PXD048212 | Pride
Project description:Chromatin Immuno-precipitaion sequencing was performed using H3-Ac, H3K4Me3, H3K9Me3, H3K27Me3, LANA, RTA and DNA Polymerase 1 alpha antibodies to investigate its enrichment on Kaposi's sarcoma associated herpesvirus (KSHV) genome in BC3 cells under normoxic or hypoxic conditions
2022-08-15 | GSE202670 | GEO
Project description:Mitochondrial dynamics are pivotal for host immune responses upon infection, yet how viruses manipulate these processes to impair host defense and enhance viral fitness remain unclear. Here we show that Kaposi's sarcoma-associated herpesvirus (KSHV), an oncogenic virus also known as human herpesvirus 8, encodes Bcl-2 (vBcl-2), which reprograms mitochondrial architecture. It binds with NM23-H2, a host nucleoside diphosphate (NDP) kinase, to stimulate GTP-loading of the dynamin-related protein (DRP1) GTPase, which triggers mitochondrial fission, inhibits mitochondrial antiviral signaling protein (MAVS) aggregation and impairs interferon responses. An NM23-H2-binding-defective vBcl-2 mutant fails to evoke fission, leading to defective virion assembly due to activated MAVS-IFN signaling. Notably, we identify two key interferon-stimulated genes restricting vBcl-2-dependent virion morphogenesis. Using a high-throughput drug screening, we discover an inhibitor targeting vBcl-2-NM23-H2 interaction that blocks virion production in vitro. Our study identifies a mechanism in which KSHV manipulates mitochondrial dynamics to allow for virus assembly, and shows that targeting the virus-mitochondria interface represents a potential therapeutic strategy
2025-04-10 | GSE292579 | GEO
Project description:The Kaposi's sarcoma associated herpesvirus (KSHV) is an oncogenic virus that causes Kaposi's sarcoma, primary effusion lymphoma (PEL), and some forms of multicentric Castleman's disease. The KSHV ORF57 protein is a conserved posttranscriptional regulator of gene expression that is essential for virus replication. ORF57 is multifunctional, but most of its activities are directly linked to its ability to bind RNA. We globally identified virus and host RNAs bound by ORF57 during lytic reactivation in PEL cells using high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP). As expected, ORF57-bound RNA fragments mapped throughout the KSHV genome, including the known ORF57 ligand PAN RNA. In agreement with previously published ChIP results, we observed that ORF57 bound RNAs near the oriLyt regions of the genome. Examination of the host RNA fragments revealed that a subset of the ORF57-bound RNAs was derived from transcript 5´ ends. The position of these 5´-bound fragments correlated closely with the 5´-most exonintron junction of the pre-mRNA. We selected four candidates (BTG1, EGR1, ZFP36, and TNFSF9) and analyzed their pre-mRNA and mRNA levels during lytic phase. Analysis of both steady-state and newly made RNAs revealed that these candidate ORF57-bound pre-mRNAs persisted for longer periods of time throughout infection than control RNAs, consistent with a role for ORF57 in pre-mRNA metabolism. In addition, exogenous expression of ORF57 was sufficient to increase the pre-mRNA levels and, in one case, the mRNA levels of the putative ORF57 targets. These results demonstrate that ORF57 interacts with specific host pre-mRNAs during lytic reactivation and alters their processing, likely by stabilizing pre-mRNAs. These data suggest that ORF57 is involved in modulating host gene expression in addition to KSHV gene expression during lytic reactivation. HITS-CLIP was performed on TREx BCBL-Rta cells 20 hpi using antibodies against ORF57. Three biological replicates were performed.
2015-02-01 | E-GEOD-64413 | biostudies-arrayexpress
Project description:Kaposi's sarcoma-associated herpesvirus (KSHV) can efficiently infect and transform primary rat mesenchymal precursor (MM) cells. Regulation of cell cycle progression and apoptosis by KSHV-encoded microRNAs is required for KSHV-induced cellular transformation and tumorigenesis.
2013-08-28 | GSE50381 | GEO