Metabolic reprogramming of Kaposi’s sarcoma associated herpes virus infected B-cells in hypoxia
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA471994 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7182252.fastq.gz | Fastqsanger.gz | |||
| SRR7182253.fastq.gz | Fastqsanger.gz | |||
| SRR7182254.fastq.gz | Fastqsanger.gz | |||
| SRR7182255.fastq.gz | Fastqsanger.gz | |||
| SRR7182256.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:We report differential gene expression in BJAB-KSHV/BJAB cells treated with Cobalt chloride/BJAB-KSHV cells treated with Cobalt Chloride compared to BJAB cells
2018-05-19 | GSE114625 | GEO
Project description:Primary human dermal endothelial cells were infected or NOT infected with isolated Kaposi's sarcoma associated herpes virus for 7 days. Total RNA was isolated using Trireagent and subjected to microarray. Keywords: other
2004-05-08 | GSE1377 | GEO
Project description:Herpesviruses are frequently co-present with bacterial infection at multiple sites within the body, including the mouth, gut, and genitourinary tract. The detection of replicating virus in these compartments prompted investigation into the relationship between bacterial infection and Kaposi’s Sarcoma-associated Herpesvirus (KSHV) reactivation. Using a cell line latently infected with KSHV, we examined the ability of crude spent media containing metabolic products from periodontal and gut pathogens to reactivate KSHV. Upon incubation with crude spent media, KSHV was reactivated and we detected the up-regulation of viral early and late genes, linear viral genomes, and virions. Furthermore, KSHV reactivation was associated with global increases in histone H3 and histone H4 acetylation, consistent with viral expression. To explore the transcriptional consequences of spent media, we compared the gene expression changes following reactivation by P. gingivalis spent medium to those of two well-established pharmacological activators of KSHV reactivation, tetradecanolyl phorbol acetate and sodium butyrate. Microarray analyses revealed a unique gene expression signature with P. gingivalis-associated reactivation. Concurrent with KSHV reactivation, P. gingivalis spent medium increased the hypoxia response. Hypoxia was associated with effects on epigenetic regulators, including down-regulation of UHRF1, a modulator of DNA methylation. Our findings demonstrate that products secreted by oral bacteria not only stimulate a hypoxia response, but also result in global changes in epigenetic modifications and modifiers. These findings suggest that epigenetic changes induced by P. gingivalis underlie the KSHV reactivation pathway.
2018-03-20 | GSE67532 | GEO
Project description:Bone Marrow Derived SH-SY5Y Neuroblastoma Cells Infected by Kaposi’s Sarcoma Herpes Virus (KSHV) Display Unique Infection Phenotypes and Growth Properties
| PRJNA725210 | ENA
Project description:Primary human dermal endothelial cells were infected or NOT infected with isolated Kaposi's sarcoma associated herpes virus for 7 days. Total RNA was isolated using Trireagent and subjected to microarray.
2008-06-12 | E-GEOD-1377 | biostudies-arrayexpress
Project description:Kaposi’s Sarcoma (KS) is a heterogenous, multifocal vascular malignancy caused by the human herpesvirus 8 (HHV8), also known as Kaposi’s Sarcoma-Associated Herpesvirus (KSHV). Here, we show that KS lesions express iNOS/NOS2 broadly throughout KS lesions, with enrichment in LANA positive spindle cells. The iNOS byproduct 3-nitrotyrosine is also enriched in LANA positive tumor cells and colocalizes with a fraction of LANA-nuclear bodies. We show that iNOS is highly expressed in the L1T3 tumor model of KS. iNOS expression correlated with KSHV lytic cycle gene expression, which was elevated in late-stage tumors (>4 weeks) but to a lesser degree in early stage (1 week) xenografts. Further, we show that L1T3 tumor growth is sensitive to an inhibitor of nitric oxide, L-NMMA. These finding suggest that iNOS is expressed in KSHV infected endothelial-transformed tumor cells in KS, that iNOS expression depends on tumor microenvironment stress conditions, and that iNOS enzymatic activity contributes to KS tumor growth.
2023-07-14 | GSE222527 | GEO
Project description:Herpesviruses are known to encode micro (mi)RNAs and to use them to regulate the expression of both viral and cellular genes. The genome of Kaposi’s sarcoma herpesvirus (KSHV) encodes a cluster of twelve miRNAs, which are abundantly expressed during both latency and lytic infection. Relatively few cellular targets of KSHV miRNAs are known. Here, we used a microarray expression profiling approach to analyze the transcriptome of both B lymphocytes and endothelial cells stably expressing KSHV miRNAs and monitor the changes induced by the presence of these miRNAs. We generated a list of potential cellular targets by looking for miRNA seed-match-containing transcripts that were significantly down regulated upon KSHV miRNAs expression. Interestingly, the overlap of putative targets identified in B lymphocytes and endothelial cells was minimal, suggesting a tissue-specific target-regulation by viral miRNAs. Among the putative targets, we identified caspase 3, a critical factor for the control of apoptosis, which we validated using luciferase reporter assays and western blotting. In functional assays we obtained further evidence that KSHV miRNAs indeed protect cells from apoptosis. Single-channel hybridization to Affymetrix oligonucleotides microarrays. DG75 and EA.hy926 cells were transducted in triplicates with the K10/12 and K12/12 lentiviral constructs expressing the KSHV miRNAs, or with a GFP-expressing construct as control. The K10/12 construct expressed only the ten intronic miRNAs miR-K12-1 to 9 and miR-K12-11 while the K12/12 construct also expressed miR-K12-10 and miR-K12-12 in addition.
2011-10-27 | E-GEOD-18946 | biostudies-arrayexpress
Project description:Kaposi's sarcoma associated herpesvirus (KSHV) infection stabilizes hypoxia inducible factors (HIFs). The interaction between KSHV encoded factors and HIFs plays a critical role in KSHV latency, reactivation and associated disease phenotypes. Besides modulation of large-scale signaling, KSHV infection also reprograms the metabolic activity of infected cells. However, the mechanism and cellular pathways modulated during these changes are poorly understood. We performed comparative RNA sequencing analysis on cells with stabilized hypoxia inducible factor 1 alpha (HIF1α) of KSHV negative or positive background to identify changes in global and metabolic gene expression. Our results show that hypoxia induces glucose dependency of KSHV positive cells with high glucose uptake and high lactate release. We identified the KSHV-encoded vGPCR, as a novel target of HIF1α and one of the main viral antigens of this metabolic reprogramming. Bioinformatics analysis of vGPCR promoter identified 9 distinct hypoxia responsive elements which were activated by HIF1α in-vitro. Expression of vGPCR alone was sufficient for induction of changes in the metabolic phenotype similar to those induced by KSHV under hypoxic conditions. Silencing of HIF1α rescued the hypoxia associated phenotype of KSHV positive cells. Analysis of the host transcriptome identified several common targets of hypoxia as well as KSHV encoded factors and other synergistically activated genes belonging to cellular pathways. These include those involved in carbohydrate, lipid and amino acids metabolism. Further DNA methyltranferases, DNMT3A and DNMT3B were found to be regulated by either KSHV, hypoxia, or both synergistically at the transcript and protein levels. This study showed distinct and common, as well as synergistic effects of HIF1α and KSHV-encoded proteins on metabolic reprogramming of KSHV-infected cells in the hypoxia.
| S-EPMC5963815 | biostudies-literature
Project description:We have reported that KSHV infection reprograms oral mesenchymal stem cells (MSCs) and transforms them to Kaposi sarcoma-like cells through mesenchymal-to-endothelial transition. To explore the mechanism of KSHV infection of MSCs, we compared the gene expression profiles of Kaposi’s sarcoma tissue and KSHV non-susceptible cells to explore potential host factors that contribute to KSHV infection.
2023-02-28 | GSE201321 | GEO
Project description:Kaposi’s Sarcoma Herpesvirus (KSHV) is the causative agent of Kaposi’s Sarcoma (KS) and isassociated with primary effusion lymphoma (PEL), multicentric Castleman’s disease (MCD) and two inflammatory diseases. KSHV-associated cancers are primarily associated with genes expressed during latency, while other pathologies are associated with lytic gene expression. The major lytic switch of the virus, RTA, interacts with cellular machinery to co-opt the host ubiquitin proteasome system to evade the immune response as well as activate the program of lytic replication. Through SILAC labeling, ubiquitin remnant enrichment and mass spectrometry, we have analyzed the RTA dependent ubiquitin-modified proteome. We identified RTA dependent changes in the populations of polyubiquitin chains, as well as changes in ubiquitinated proteins in both cells expressing RTA and naturally infected cells following lytic reactivation. We observed an enrichment of proteins that are also reported to be SUMOylated, suggesting that RTA, a SUMO targeting ubiquitin ligase, may function to alleviate a SUMO dependent block to lytic reactivation. RTA targeted substrates directly through a ubiquitin ligase domain dependent mechanism as well as indirectly through cellular ubiquitin ligases, including RAUL. Our ubiquitome analysis revealed an RTA dependent mechanism of immune evasion. We provide evidence of inhibition of TAP dependent peptide transport, resulting in decreased HLA complex stability. The results of this analysis increase our understanding of mechanisms governing the latent to lytic transition in addition to the identification of a novel RTA dependent mechanism of immune evasion.Kaposi’s Sarcoma Herpesvirus (KSHV) is the causative agent of Kaposi’s Sarcoma (KS) and is associated with primary effusion lymphoma (PEL), multicentric Castleman’s disease (MCD) and two inflammatory diseases. KSHV-associated cancers are primarily associated with genes expressed during latency, while other pathologies are associated with lytic gene expression. The major lytic switch of the virus, RTA, interacts with cellular machinery to co-opt the host ubiquitin proteasome system to evade the immune response as well as activate the program of lytic replication. Through SILAC labeling, ubiquitin remnant enrichment and mass spectrometry, we have analyzed the RTA dependent ubiquitin-modified proteome. We identified RTA dependent changes in the populations of polyubiquitin chains, as well as changes in ubiquitinated proteins in both cells expressing RTA and naturally infected cells following lytic reactivation. We observed an enrichment of proteins that are also reported to be SUMOylated, suggesting that RTA, a SUMO targeting ubiquitin ligase, may function to alleviate a SUMO dependent block to lytic reactivation. RTA targeted substrates directly through a ubiquitin ligase domain dependent mechanism as well as indirectly through cellular ubiquitin ligases, including RAUL. Our ubiquitome analysis revealed an RTA dependent mechanism of immune evasion. We provide evidence of inhibition of TAP dependent peptide transport, resulting in decreased HLA complex stability. The results of this analysis increase our understanding of mechanisms governing the latent to lytic transition in addition to the identification of a novel RTA dependent mechanism of immune evasion.
2024-11-24 | PXD046571 | Pride