Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hijacking of Nucleotide Biosynthesis and Deamidation-mediated Glycolysis by an Oncogenic Herpesvirus

ABSTRACT: Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma (KS) and multiple types of B cellmalignancies. Emerging evidence demonstrates that KSHV reprograms host-cell central carbon metabolic pathways, which contributesto viral persistence and tumorigenesis. However, the mechanisms underlying KSHV-mediated metabolic reprogramming remain poorlyunderstood. Carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase (CAD) is a key enzyme of the denovo pyrimidine synthesis, and was recently identified to deamidate the NF-κB subunit RelA to promote aerobic glycolysis and cellproliferation. Here we report that KSHV infection exploits CAD for nucleotide synthesis and glycolysis. Mechanistically, KSHV vCyclin binds to and hijacks cyclin-dependent kinase CDK6 to phosphorylate Ser-1900 on CAD, thereby activating CAD-mediatedpyrimidine synthesis and RelA-deamidation-mediated glycolytic reprogramming. Correspondingly, genetic depletion orpharmacological inhibition of CDK6 and CAD potently impeded KSHV lytic replication and thwarted tumorigenesis of primaryeffusion lymphoma (PEL) cells in vitro and in vivo. Altogether, our work defines a viral metabolic reprogramming mechanismunderpinning KSHV oncogenesis, which may spur the development of new strategies to treat KSHV-associated malignancies and otherdiseases.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Kidney Cell

DISEASE(S): Kaposi's Sarcoma

SUBMITTER: Jun Zhao

LAB HEAD: Jun Zhao

PROVIDER: PXD043435 | Pride | 2024-02-16

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	2020071613-K6-1.raw	Raw
	2020071613-K6-2.raw	Raw
	2020071613-K6-3.raw	Raw
	2020071613-K6-4.raw	Raw
	2020071613-Vec-1.raw	Raw

Items per page:

1 - 5 of 13

Similar Datasets

Expression data of extracellular vesicles from kaposi's sarcoma associated herpesvirus- or mock- infected human endothelial cells treated human endothelial cell

Project description:Kaposi’s Sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi’s sarcoma, which is the most common cancer in acquired immune deficiency syndrome patients. Because KSHV has many viral proteins modulate many response, However, various effects by extracellular vesicles (EVs) during de novo KSHV infection has not been investigated to our best knowledge. We used microarrays to detail of gene expression underlying EV treatment and identified the up-regulated genes during treatment.

2018-10-16 | GSE121220 | GEO

The effect of ORF57 knockout (KO) on host expression in iSLK/Bac16 cells.

Project description:Kaposi’s sarcoma-associated herpesvirus (KSHV) is a human oncogenic virus associated with various malignancies, including Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. The expression of viral products is essential for initiating and sustaining KSHV-induced tumors. KSHV ORF57, a viral RNA-binding protein, plays a crucial role in regulating viral gene expression at the posttranscriptional level by promoting viral RNA stability, splicing, and translation. In addition, ORF57 dysregulates host gene expression to promote viral replications.

2024-11-21 | GSE259446 | GEO

RNA-seq of two Kaposi’s sarcoma tissue samples and the corresponding two normal tissue samples

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

KSHV uses viral IL6 to expand infected immunosuppressive macrophages (scRNA-seq)

Project description:Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic double-stranded DNA virus and the etiologic agent of Kaposi’s sarcoma and hyperinflammatory lymphoproliferative disorders. Understanding the mechanism by which KSHV increases infected cell populations is crucial for curing KSHV-associated diseases. Here, we demonstrate that KSHV preferentially infects CD14+ monocytes and sustains viral replication through the viral interleukin-6 (vIL-6)-mediated activation of STAT1 and 3. Using vIL6-sufficient and vIL6-deficient recombinant KSHV, we demonstrated that vIL6 plays a critical role in promoting the proliferation and differentiation of KSHV-infected monocytes into macrophages. The macrophages derived from vIL6-sufficient (wild type) KSHV infection showed a distinct transcriptional profile of elevated IFN-pathway activation with immune suppression and were compromised in T-cell stimulation function compared to those from vIL6-deficient KSHV infection or uninfected control. These results highlight a clever strategy, in which KSHV utilizes vIL6 to secure its initial viral pool by expanding infected dysfunctional macrophages. This mechanism also facilitates KSHV to escape from host immune surveillance and to establish a lifelong infection.

2023-08-30 | GSE227166 | GEO

KSHV uses viral IL6 to expand infected immunosuppressive macrophages (RNA-seq)

2023-08-30 | GSE227163 | GEO

Integrated Systems Biology Analysis of KSHV Latent Infection Reveals Viral Induction and Reliance on Peroxisome Mediated Lipid Metabolism

Project description:Kaposi’s Sarcoma herpesvirus (KSHV), an oncogenic virus, modulates host cell signaling and metabolism to maintain latent infection. To unravel the underlying cellular mechanisms modulated by KSHV, we identified changes in the host proteome, phosphoproteome and transcriptome landscape upon KSHV infection of endothelial cells. A Steiner Forest algorithm was used to integrate proteomic, phosphoproteomic and transcriptomic data with transcriptome based predicted transcription factor activity to identify cellular networks altered by latent KSHV.

2017-02-08 | GSE84237 | GEO

Epstein–Barr virus (EBV) Rta-mediated cell cycle arrest enables permissive replication of EBV and Kaposi’s sarcoma-associated herpesvirus in 293 cells

Project description:Epstein-Barr virus (EBV) Rta is a latent-lytic molecular switch evolutionarily conserved in all gamma-herpesviruses. In previous studies, doxycycline-inducible Rta was shown to potently produce an irreversible G1 arrest followed by cellular senescence in 293 cells. Here, we demonstrate that in this system the inducible Rta not only reactivates resident genome of EBV but also that of Kaposi’s sarcoma-associated herpesvirus (KSHV), to similar efficiency. However, Rta-induced senescence program was terminated by the robust viral lytic cycle replication that eventually caused cell death. Furthermore, prior to the abrupt expression of immediate-early protein (EBV BZLF1 or KSHV RTA), Rta simultaneously down-regulates cell cycle activators (c-Myc, CDK6, CCND2) and up-regulates senescence-related genes (p21, 14-3-3s). Since Rta is a viral immediate-early transcriptional activator, it is envisioned that during the initial stage of viral reactivation, Rta may engage to modulate the host transcriptome, to halt cell cycle progression, and to maintain an ideal environment for manufacturing infectious virions. Refer to individual Series. This SuperSeries is composed of the following subset Series: GSE24585: Expression profiling of host genes modulated by Epstein-Barr virus (EBV) Rta in HEK293 cells GSE24586: Expression profiling of host genes modulated by Epstein-Barr virus Rta in nasopharyngeal carcinoma cells

2011-03-31 | E-GEOD-24587 | biostudies-arrayexpress

mRNA Sequencing of BC-1 Cells

Project description:Kaposi’s sarcoma-associated herpesvirus (KSHV) causes the B cell malignancy primary effusion lymphoma (PEL). Here we performed mRNA sequencing to characterize the mRNA expression profile of the primary effusion lymhoma (PEL) cell line BC-1.

2022-08-10 | GSE210446 | GEO

Kinome profiling of Non-Hodgkin Lymphoma identifies Tyro3 as a therapeutic target in PEL

Project description:Non-Hodgkin lymphomas (NHL) make up the majority of lymphoma diagnoses and represent a very diverse set of malignancies. We sought to identify kinases uniquely upregulated in different NHL subtypes. Using Multiplexed Inhibitor Bead-mass spectrometry (MIB/MS), we found Tyro3 was uniquely upregulated and important for cell survival in primary effusion lymphoma (PEL), which is a viral lymphoma infected with Kaposi’s sarcoma-associated herpesvirus (KSHV).

2019-07-11 | PXD012087 | Pride

Differentially regulated splice variants and systems biology analysis of Kaposi's Sarcoma-associated Herpesvirus-infected lymphatic endothelial cells

Project description:Alternative RNA splicing greatly increases proteome diversity, and the possibility of studying genome-wide alternative splicing (AS) events becomes available with the advent of high-throughput genomics tools devoted to this issue. Kaposi’s sarcoma associated herpesvirus (KSHV) is the etiological agent of KS, a tumor of lymphatic endothelial cell (LEC) lineage, but little is known about the AS variations induced by KSHV. We analyzed KSHV-controlled AS using high-density microarrays capable of detecting all exons in the human genome. Splicing variants and altered exon-intron usage in infected LEC were found, and these correlated with protein domain modification. The different 3’ UTR used in new transcripts also help isoforms to escape microRNA-mediated surveillance. Exome-level analysis further revealed information that cannot be disclosed using classical gene-level profiling: a significant exon usage difference existed between LEC and CD34+ precursor cells, and KSHV infection resulted in LEC-to-precursor, dedifferentiation-like exon level reprogramming. Our results demonstrate the application of exon arrays in systems biology research, and suggest the regulatory effects of AS in endothelial cells are far more complex than previously observed. This extra layer of molecular diversity helps to account for various aspects of endothelial biology, KSHV life cycle and disease pathogenesis that until now have been unexplored. 5 samples were analyzed. 3 were KSHV infected lymphatic endothelial cells (LECs), and 2 were non-infected control samples.

2011-05-05 | E-GEOD-26341 | biostudies-arrayexpress

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