VZV infection of primary keratinocytes
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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: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: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:Analysis of growing or oncogene-induced senescent primary mouse keratinocytes 6 days post infection.
2017-01-13 | GSE93564 | GEO
Project description:HPV alters the host transcriptional program to establish infection and complete its lifecycle. Infection of keratinocytes has been difficult until our development of extracellular matrix (ECM) to cell transfer system that allows efficient infection of primary keratinocytes. Using this model, the transcriptional program of HPV infected keratinocytes at different times post infection was analyzed by mRNA-seq.
2019-11-10 | GSE137361 | GEO
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare transcriptome profiling (RNA-seq) between Primary Keratinocytes and OSM-treated Primary Keratinocytes Methods: mRNA profiles of Primary Keratinocytes and OSM-treated Primary Keratinocytes were generated by deep sequencing, in triplicate, using Illumina GAIIx. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks.
2021-03-18 | GSE151174 | GEO
Project description:We aim to analyze the transcriptional profiles of primary human keratinocytes in response to interferon gamma (IFNG) treatment and/or HSV-2 (strain HG-52) infection. The goal is to define IFNG regulated intrinsic immunity of primary human keratinocytes and how HSV-2 infection regulates the intrinsic immunity of primary human keratinocyte.
2021-04-21 | GSE172424 | GEO
Project description:HPV alters the host transcriptional program to establish infection and complete its lifecycle. Infection of keratinocytes has been difficult until our development of extracellular matrix (ECM) to cell transfer system that allows efficient infection of primary keratinocytes. Using this model, the transcriptional program of HPV infected keratinocytes grown in raft culture was analyzed by mRNA-seq.
2019-11-10 | GSE137964 | GEO
Project description:In adult K14Î?NLef1 mouse, the overexpression of â??NLef1, a Ã?-catenin dominat negative, in basal keratinocytes leads to the conversion of hair follicles into multilayered epithelial cysts and ectopic sebaceous gland. â??NLef1 transcriptional activity led to Gata6 overexpression in the pilosebaceous unit in transgenic mice. To uncover direct target genes of Gata6 we performed ChIP-Seq experiments in primary mouse keratinocytes. Examination of Gata6 genomic targets in mouse primary keratinocytes
2017-05-16 | E-GEOD-62607 | biostudies-arrayexpress