Single cell sequencing of VZV gE antigen-specific T cells with vaccination and age
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE286045 | GEO | 2025/11/14
REPOSITORIES: GEO
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Project description:Single cell sequencing of VZV gE antigen-specific T cells with vaccination and age
| PRJNA1207543 | ENA
Project description:SHINGRIX vaccination was used to investigate the fate of antigen specific memory CD4+ T cell at both cellular and transcriptional level upon immunization in a one-year longitudinal study. SHINGRIX is a subunit vaccine with glycoprotein E (gE) of varicella zoster virus (VZV) as the immunogen and requires two doses at least 60 days apart for protection against Herpes Zoster in adults over 50 years old. Flow cytometry and single-cell RNA sequencing were used to evaluate cellular and transcriptomic changes of VZV gE epitope-specific CD4+ T cells in a TCR clonotypic fashion pre and post vaccination. Antigen-specific T cells remained at a higher frequency compared to baseline and retained markers of cell activation such as ICOS and PD1 even one year post-vaccination. Persistent TCR clonotypes amongst epitope-specific T-cells were common across different time points within each individual. Antigen-specific memory T cells with a dominant TCR clonotype at baseline remained at a relatively high frequency one year later after two doses of vaccine. In contrast, T cells with TCR clonotypes from naïve antigen specific cells at baseline could not be detected post-vaccination. Differential gene expression analyses of cells with identical TCR clonotypes show that cells post vaccination, including those at one year post vaccination, were distinct from cells at baseline, with upregulation of genes related to T cell differentiation, negative T cell regulation and T cell activation. Thus, in addition to an increase in frequency, committed memory T cells gain additional transcriptional changes upon vaccination that could alter the immune response against cognate immunogens compared to pre-vaccinated quiescent memory T cells.
2025-03-09 | GSE249632 | GEO
Project description:Aging trajectories of antigen-specific memory T cells are heterogenous and complex but incompletely understood. We use single-cell sequencing of EBV (Epstein Barr virus)- or VZV (Varicella Zoster virus)-antigen specific T cells of younger or older adults to analyze memory T cell heterogeneity in early and late life.
2025-06-01 | GSE275634 | GEO
Project description:Aging trajectories of antigen-specific memory T cells are heterogenous and complex but incompletely understood. We use single-cell sequencing of EBV (Epstein Barr virus)- or VZV (Varicella Zoster virus)-antigen specific T cells of younger or older adults to analyze memory T cell heterogeneity in early and late life.
2025-06-01 | GSE275633 | 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: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: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:Influenza imparts an age-related increase in mortality and morbidity. The most effective countermeasure is vaccination; however, vaccines offer modest protection in older adults. To investigate how ageing impacts the memory B cell response we tracked haemagglutinin specific B cells by indexed flow sorting and single cell RNA sequencing in twenty healthy adults administered the trivalent influenza vaccine. We found age-related skewing in the memory B cell compartment six weeks after vaccination, with younger adults developing haemagglutinin specific memory B cells with an FCRL5+ “atypical” phenotype, showing evidence of somatic hypermutation and positive selection, which happened to a lesser extent in older persons. We confirmed the germinal center ancestry of these FCRL5+ “atypical” memory B cells using scRNASeq from fine needle aspirates of influenza responding human lymph nodes and paired blood samples. Together, this study shows that the aged human germinal center reaction and memory B cell response following vaccination is defective.
2021-03-05 | GSE167823 | 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 | GSE206641 | GEO