Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE227166 | GEO | 2023/08/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

KSHV uses viral IL6 to expand infected immunosuppressive macrophages (RNA-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 | GSE227163 | GEO

TREx-BCBL1-RTA GPRC5A-FLAG Immunoprecipitation LC-MS

Project description:The epitranscriptomic modification m6A is a ubiquitous feature of the mammalian transcriptome. It modulates mRNA fate and dynamics to exert regulatory control over numerous cellular processes and disease pathways, including viral infection. Kaposi’s sarcoma-associated herpesvirus (KSHV) reactivation from the latent phase leads to redistribution of m6A topology upon both viral and cellular mRNAs within infected cells. Here we investigate the role of m6A in cellular transcripts upregulated during KSHV lytic replication. Results show that m6A is crucial for the stability of the GPRC5A mRNA, whose expression is induced by the KSHV latent-lytic switch master regulator, the replication and transcription activator (RTA) protein. Moreover, we demonstrate that GPRC5A is essential for efficient KSHV lytic replication by directly regulating NFκB signalling. Overall, this work highlights the central importance of m6A in modulating cellular gene expression to influence viral infection.

2023-07-20 | PXD039669 | Pride

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

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

Project description: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.

2024-02-16 | PXD043435 | Pride

Quantitative proteomics analysis of lytic KSHV infection in human endothelial cells reveals novel targets of viral immune modulation

Project description:Kaposi’s Sarcoma associated herpesvirus (KSHV) is an oncogenic human virus and leading cause of mortality in HIV infection. Reactivation of KSHV from latent to lytic stage infection initiates a cascade of viral gene expression, and here we show how these changes remodel the host cell proteome to enable viral replication. By undertaking a systematic and unbiased analysis of changes to the endothelial cell proteome following lytic KSHV reactivation, we quantify >7000 cellular and 71 viral proteins. Lytic KSHV infection resulted in >2-fold downregulation of 291 cellular proteins, including PKR, the key cellular sensor of double-stranded RNA. A complementary KSHV genome-wide CRISPR genetic screen identified K5 as the viral gene responsible for the downregulation of two novel KSHV targets, Nectin-2 and CD155, both ligands of the NK cell DNAM-1 receptor. Despite the high episome copy number, we show that CRISPR Cas9 provides a remarkably efficient way to target KSHV genomes.

2021-08-23 | PXD021387 | Pride

Quantitative proteomics analysis of lytic KSHV infection in human endothelial cells reveals novel targets of viral immune modulation

2022-05-26 | PXD017365 | Pride

KSHV Infection Mimics the Hypoxic Response Based on Next-Generation Sequencing [miRNA-Seq]

Project description:Purpose: Kaposi’s sarcoma associated-herpesvirus (KSHV) causes several hyperproliferative disorders, including Kaposi’s sarcoma, primary effusion lymphoma and multicentric Castleman’s disease. KSHV encodes for a number of microRNAs (miRNAs), and KSHV infection can affect the expression of cellular miRNAs. Hypoxia has been shown to induce KSHV reactivation, directly induce several KSHV lytic genes, and also induce the most abundant latent viral protein, LANA. Also, several KSHV proteins can stabilize and increase the cellular levels of hypoxia-inducible factor (HIF-1α). However, the degree to which hypoxic pathways are utilized by KSHV has yet to be determined. Methods: We investigated the interplay between hypoxia and KSHV infection by comparing the 31effects of hypoxia and KSHV infection on miRNA and mRNA expression, and by examining the 32effects of hypoxia on uninfected and KSHV-infected cells. This was accomplished using next-33generation sequencing (NGS), qRT-PCR, Taqman assays, and pathway analysis. Results: NGS analysis of human mRNAs revealed striking similarities (~34%) between the transcriptomic response to hypoxia and the transcriptomic response to KSHV infection. Additionally, hsa-miR-210, a key hypoxia-inducible miRNA with pro-angiogenic and anti-apoptotic properties, was found significantly up-regulated by both KSHV infection and hypoxia using Taqman assays. Finally, KSHV infected cells differed somewhat in their response to hypoxia compared to KSHV-uninfected controls. Conclusions: These results demonstrate that KSHV harnesses a part of the hypoxic cellular response and induces miR-210 up-regulation. The understanding of how these miRNAs, genes and pathways are regulated by HIF-1α and KSHV infection are essential to a better understanding of the biology of KSHV-associated diseases.

2016-12-21 | GSE79030 | GEO

KSHV Infection Mimics the Hypoxic Response Based on Next-Generation Sequencing [mRNA-Seq]

2016-12-21 | GSE79029 | 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

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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