Comparison the transcriptional changes in the mutation of VZV circVLTs
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE223957 | GEO | 2024/04/27
REPOSITORIES: GEO
Similar Datasets
Project description:Varicella-zoster virus (VZV), an alphaherpesvirus, causes chickenpox (varicella) in young children with an annual minimum of 140 million new cases and herpes zoster in senior, a painful and debilitating disease with 3-5‰ incidence. A complex structural transcriptome of VZV, which numerous novel transcripts, transcript isoforms, and unknown splice events are found during cell infection. Circular RNA (circRNA), a newly important component of the transcriptome, is increasing discoveries of circRNA function in mammalian cells. However, VZV encoded circRNA remains unexplored. The code used in this study and extended data are available from the GitHub repository (https://github.com/ShaominYang/VZV_circRNA)
2024-04-27 | GSE252124 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Useful links: Parsed data: (ftp://ftp.ebi.ac.uk/pub/databases/scnmt_gastrulation) Github repository: (https://github.com/rargelaguet/scnmt_gastrulation)
2019-09-30 | GSE121708 | GEO
Project description:The highly conserved herpesvirus glycoprotein complex, gB/gH-gL, mediates membrane fusion during virion entry and cell-cell fusion. Varicella-zoster virus (VZV) characteristically forms multi-nucleated cells, or syncytia, during the infection of human tissues but little is known about this process. The cytoplasmic domain of VZV gB (gBcyt) has been implicated in cell-cell fusion regulation because a gB[Y881F] substitution causes hyperfusion. The gBcyt regulation is necessary for VZV pathogenesis as the hyperfusogenic mutant gB[Y881F] is severely attenuated in human skin xenografts. In this study, gBcyt regulated fusion was investigated by comparing melanoma cells infected with wild type-like VZV or hyperfusogenic mutants. The gB[Y881F] mutant exhibited dramatically accelerated syncytia formation in melanoma cells caused by fusion of infected cells with many uninfected cells, increased cytoskeleton reorganization and rapid displacement of nuclei to dense central structures when compared to pOka using live cell confocal microscopy. VZV and human transcriptomes were concurrently investigated using RNA-seq to identify viral and cellular responses induced when the gBcyt regulation was disrupted by the gB[Y881F] substitution. The expression of four vital VZV genes, ORF61 and glycoproteins, gC, gE and gI, was significantly reduced at 36 hours post infection for the hyperfusogenic mutants. Importantly, hierarchical clustering demonstrated an association of differential gene expression with dysregulated gBcyt-mediated fusion. A subset of Ras GTPase genes linked to membrane remodeling were upregulated in cells infected with the hyperfusogenic mutants. These data implicate the gBcyt in the regulation gB fusion function that, if unmodulated, triggers cellular processes leading to hyperfusion that attenuates VZV infection.
2017-03-01 | GSE85493 | GEO
Project description:Our aim was to investigate the interaction between epidermal differentiation and VZV infection. By means of a calcium-induced keratinocyte differentiation model and RNA-seq we show VZV infection has a profound effect on differentiating keratinocytes and hijacks the normal process of epidermal gene expression to generate a signature resembling patterns of gene expression seen in both heritable and acquired skin-blistering disorders. Analysis of the viral transcriptome provides evidence that VZV replication in skin is tightly linked to differentiation and critically, that late viral gene expression is associated with cellular differentiation. The experiment was performed on human primary keratinocytes under four conditions: undifferentiated/uninfected, uninfected/differentiated, VZV-infected/undifferentiated and VZV-infected/differentiated.
2014-05-29 | E-MTAB-1717 | biostudies-arrayexpress
Project description:Exosomes have emerged as essential extracellular signaling vesicles that can deliver proteins and nucleic acids to cells during normal and disease states. Herein, we studied the effects of exosomes produced by VZV-infected human sensory neurons on cerebrovascular cells. Exosomes were isolated from mock- and VZV-infected sensory neurons and protein and nucleic acid was determined by mass spectrometry and Next-Generation Sequencing. Subsequently, mock- and VZV-derived exosomes were applied to primary human brain vascular adventitial fibroblasts (HBVAFs). Overall, exosomes from VZV-infected sensory neurons impacted the pro-inflammatory phenotype of HBVAF cells. The presence of pathogenic exosomes that could circulate throughout the body provides insight into clinical infections.
2024-06-28 | GSE206641 | GEO
Project description:During primary infection, varicella-zoster virus (VZV) is spread via lymphocytes to skin, where it induces a rash and establishes latency in sensory ganglia. A live, attenuated varicella vaccine (vOka) was generated by using the VZV Oka strain (pOka), but the molecular basis for vOka attenuation remains unknown. Little is known concerning the effects of wild-type or attenuated VZV on cellular gene regulation in the host cells that are critical for pathogenesis. In this study, transcriptional profiles of primary human T cells and fibroblasts infected with VZV in cell culture were determined by using 40,000-spot human cDNA microarrays. Cellular gene transcription in human skin xenografts in SCID mice that were infected with VZV in vivo was also evaluated. The profiles of cellular gene transcripts that were induced or inhibited in infected human foreskin fibroblasts (HFFs), T cells, and skin in response to pOka and vOka infection were similar. However, significant alterations in cellular gene regulation were observed among the three differentiated human cell types that were examined, suggesting specific differences in the biological consequences of VZV infection related to the target cell. Changes in cellular gene transcription detected by microarray analysis were confirmed for selected genes by quantitative real-time reverse transcription-PCR analysis of VZV-infected cells. Interestingly, the transcription of caspase 8 was found to be decreased in infected T cells but not in HFFs or skin, which may signify a tissue-specific antiapoptosis mechanism. The use of microarrays to demonstrate differences in effects on host cell genes in primary, biologically relevant cell types provides background information for experiments to link these various response phenotypes with mechanisms of VZV pathogenesis that are important for the natural course of human infection.
2005-10-07 | E-SMDB-1945 | biostudies-arrayexpress
Project description:Varicella Zoster Virus (VZV) is a skin-tropic virus that infects epidermal keratinocytes and causes chickenpox. Although common, VZV infection can be life-threatening particularly in the immunocompromised. Therefore, understanding VZV-keratinocyte interactions is important to find new treatments beyond vaccination and anti-viral drugs. In VZV- infected skin, Kallikrein 6 (KLK6), and the ubiquitin-ligase MDM2 are up-regulated concomitant with Keratin 10 (K10) down-regulation. MDM2 binds to K10 targeting it for degradation via the ubiquitin-proteasome pathway. Preventing K10 degradation reduced VZV propagation in culture and prevented epidermal disruption in skin explants. K10 knockdown induced expression of the nuclear receptor subfamily 4, group A, member 1 (NR4A1) and enhanced viral propagation in culture. NR4A1 knockdown prevented viral propagation in culture, reduced LC3 levels and increased LAMP2 expression. We therefore describe a novel drug-able pathway whereby MDM2 ubiquitinates and degrades K10 increasing NR4A1 expression allowing VZV replication and propagation.
2019-08-29 | GSE136586 | GEO
Project description:Exosomes have emerged as essential extracellular signaling vesicles that can deliver proteins and nucleic acids to cells during normal and disease states. Herein, we studied the effects of exosomes produced by VZV-infected human sensory neurons on cerebrovascular cells. Exosomes were isolated from mock- and VZV-infected sensory neurons and protein and nucleic acid was determined by mass spectrometry and Next-Generation Sequencing. Subsequently, mock- and VZV-derived exosomes were applied to primary human brain vascular adventitial fibroblasts (HBVAFs). Overall, exosomes from VZV-infected sensory neurons impacted the pro-inflammatory phenotype of HBVAF cells. The presence of pathogenic exosomes that could circulate throughout the body provides insight into clinical infections.
2024-06-28 | GSE206642 | GEO
Project description:Varicella-zoster virus (VZV), an alphaherpesvirus, causes chickenpox (varicella) in young children with an annual minimum of 140 million new cases and herpes zoster in senior, a painful and debilitating disease with 3-5‰ incidence. A complex structural transcriptome of VZV, which numerous novel transcripts, transcript isoforms, and unknown splice events are found during cell infection. Circular RNA (circRNA), a newly important component of the transcriptome, is increasing discoveries of circRNA function in mammalian cells. However, VZV encoded circRNA remains unexplored. In this study we demonstration that VZV derived circRNAs are biologically functional and contributed to viral pathogenesis. Using deep RNA-seq following RNase R treatment, we identified and charactered 35, 076 and 54 human and VZV pOka strain circRNAs respectively from VZV infected neuroblastoma cell (SH-SY5Y).
2024-04-27 | GSE223870 | GEO