Deletion of HCMV US17 alters host immune genes at 12 hpi and ER stress genes at 96 hpi.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Philip Pellett
PROVIDER: E-GEOD-50955 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Infection of human fibroblasts with either human cytomegalovirus strain AD169 or a recombinant virus deleted for HCMV US17 Illumina HT-12 beadarrays were used to quantitate levels of host transcripts at either 12 or 96 hpi.
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Project description:Human cytomegalovirus induces a pro-inflammatory monocyte following infection. To begin to address how HCMV induces these rapid changes in infected monocytes, we examined the transcriptome of infected monocytes. Global transcriptional profiling using cDNA microarrays revealed a significant number of pro-inflammatory genes were upregulated within 4 hours post infection. Experiment Overall Design: To begin to globally define the HCMV-induced changes in monocyte function, we performed a transcriptome analysis. Specifically, a cDNA microarray containing 12,626 unique probe sets was utilized to assess the modulation of the monocyte transcriptome at 4 hours post infection. A total of 6 replicates from mock-infected and 6 replicates from HCMV-infected monocytes were analyzed in this study.
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Project description:human foreskin fibroblasts were infected with HCMV We monitor cellular gene expression network altered by HCMV entry using Affymetrix Human Genome U133 Plus 2.0 Array 2 time points were measured, 5min, 25min
2013-03-15 | E-GEOD-27974 | biostudies-arrayexpress
Project description:Human cytomegalovirus (HCMV) induces pro-inflammatory monocytes following infection and we have evidence that EGFR is a key mediator in this early activation. To begin to address how this signalling pathway is responsible for the rapid activation of infected monocytes, we examined the role this pathway played in the transcriptome of infected monocytes. Global transcriptional profiling using cDNA microarrays revealed a significant number of genes, including inflammatory genes, were regulated in a EGFR-dependent manner, identifying this pathway as a key cellular control point in the conversion of monocytes to an activated pro-inflammatory state following HCMV infection. Keywords: Disease state To begin to globally define how EGFR is involved in the HCMV-induced changes in monocyte function, we performed a transcriptome analysis in the presence of inhibitors to the EGFR signalling pathway. Specifically, a cDNA microarray containing 12,625 unique probe sets was utilized to assess the modulation of the monocyte transcriptome at 24 hours post infection in the presence of blocking anti-EGFR antibody and pharmacological agent AG1478 (AG; an EGFR inhibitor). A total of 4 replicates from mock-infected, HCMV-infected, anti-EGFR antibody-pretreated infected and AG-pretreated infected monocytes were analyzed in this study.
2009-09-03 | E-GEOD-17948 | biostudies-arrayexpress
Project description:Human cytomegalovirus induces a pro-inflammatory monocyte following infection and we have evidence that NF-κB and phosphatidylinositol 3-kinase [PI(3)K] are key mediators in this early activation. To begin to address how these signalling pathways are responsible for the rapid activation of infected monocytes, we examined the role these pathways played in the transcriptome of infected monocytes. Global transcriptional profiling using cDNA microarrays revealed a significant number of genes, including inflammatory genes, were regulated in a NF-κB- and/or PI(3)K-dependent manner, identifying these pathways as key cellular control points in the conversion of monocytes to an activated pro-inflammatory state following HCMV infection. Experiment Overall Design: To begin to globally define how NF-κB and PI(3)K are involved in the HCMV-induced changes in monocyte function, we performed a transcriptome analysis in the presence of inhibitors to NF-κB and PI(3)K signalling pathways. Specifically, a cDNA microarray containing 12,626 unique probe sets was utilized to assess the modulation of the monocyte transcriptome at 4 hours post infection in the presence of the pharmalogical agents Bay11-7082 (Bay11; a NF-κB inhibitor) and LY294002 (LY; a PI(3)K inhibitor). A total of 6 replicates from HCMV-infected monocytes, 3 replicates from Bay11-pretreated infected monocytes and 3 replicates from LY-pretreated infected monocytes were analyzed in this study.
2008-06-16 | E-GEOD-9601 | biostudies-arrayexpress
Project description:Human cytomegalovirus (HCMV) induces pro-inflammatory monocytes following infection and we have evidence that phosphatidylinositol 3-kinase [PI(3)K] is a key mediator in this activation. To begin to address how this signalling pathway is responsible for the functional changes in infected monocytes, we examined the role this pathway played in the transcriptome of infected monocytes. Global transcriptional profiling using cDNA microarrays revealed a significant number of genes were regulated in a PI(3)K-dependent manner, identifying this pathway as a key cellular control point in the conversion of monocytes to an activated pro-inflammatory state following HCMV infection. Keywords: Disease state To begin to globally define how PI(3)K is involved in the HCMV-induced changes in monocyte function, we performed a transcriptome analysis in the presence of an inhibitor to the PI(3)K signalling pathway. Specifically, a cDNA microarray containing 12,626 unique probe sets was utilized to assess the modulation of the monocyte transcriptome at 48 hours post-infection in the presence of the pharmacological agent LY294002 (LY), a PI(3)K inhibitor. A total of 2 replicates from HCMV-infected monocytes, 2 replicates from LY-pretreated infected monocytes, and 2 replicates from mock-infected monocytes were analyzed in this study.
2010-01-06 | E-GEOD-19772 | biostudies-arrayexpress
Project description:Human cytomegalovirus (HCMV) is a significant cause of disease in immune-compromised adults and immune naïve newborns. No vaccine exists to prevent HCMV infection, and current antiviral therapies have toxic side effects that limit the duration and intensity of their use. There is thus an urgent need for new strategies to treat HCMV and repurposing existing drugs as antivirals is an attractive approach. Virus-induced changes in infected cells are often driven by changes in cellular kinase activity, leading us to hypothesize that defining the complement of kinases (the kinome), whose activity or expression is altered during infection would identify existing kinase inhibitors that could be repurposed as new antivirals. To this end, we applied a recently developed technique, MIB-MS kinome profiling, to quantitatively measure perturbations in >240 cellular kinases simultaneously in cells infected with a laboratory-adapted (AD169) or clinical (TB40E) HCMV strain using a label-free approach. Significant time-dependent changes for multiple kinases including cell cycle, receptor tyrosine and mitotic kinases were observed. Based on these data, we tested antiviral activity of 14 kinase inhibitors, and the most potent inhibitor blocked HCMV early gene expression and viral DNA accumulation. These results show the utility of kinome profiling to screen kinase inhibitors that can be repurposed as antivirals.
2017-03-20 | PXD005276 | Pride
Project description:HCMV -treated and control human adult neural precurso cells (NPC) were used to extract RNA for profiling on DNA arrays Primary adult hippocampus-derived neural precursor cells were used at passage # 2-4 for HCMV infection, followed by RNA extraction at indicated times Primary adult neural precursor cells were infected with HCMV strains Towne and TR (O.1MOI) and RNA was extracted at 72 hrs postinfection for expression profiling on both HCMV and Affymetrix DNA arrays
2012-07-21 | E-GEOD-30912 | biostudies-arrayexpress
Project description:Infection or reactivation with human cytomegalovirus (HCMV) is still a major cause of morbidity and mortality in patients undergoing solid organ transplantation or allogeneic stem cell transplantation (alloSCT). Recent studies have shown that protection against latent HCMV infection relies on a much broader antigen spectrum than previously expected. The identification of novel immunogenic HCMV-derived peptides that facilitate HCMV control is therefore essential to improve immune monitoring of HCMV-specific T cells and HCMV vaccine development. In particular, only a few HCMV-derived peptides have been described for less common HLA alleles, such as HLA-A*03:01 and HLA-B*15:01, limiting the implementation of these techniques for a substantial number of patients. Here, we identified novel HCMV-derived HLA-A*03:01- and HLA-B*15:01-restricted immunogenic peptides by an innovative combined in vitro and in silico approach. We utilized the computational tools Peptide-PRISM (1) and PRICE (2) to analyze mass spectrometric (MS) and ribosome sequencing (ribo-seq) datasets, respectively. To refine our in silico approach, we utilized machine learning to rate the identified peptide candidates based on their translational activity, binding affinity and positioning within the small open reading frames (sORFs), with the goal of assessing their likelihood to be presented on HLA-A*03:01 and HLA-B*15:01 molecules. After identifying the highest-scoring 49 canonical and 49 cryptic potentially immunogenic peptides for each HLA allele, we assessed their immunogenicity by screening HCMV-seropositive and -seronegative healthy donors, as well as alloSCT patients for their peptide-specific T-cell responses. We used a stimulation procedure in two consecutive steps: peripheral blood cells (PBMCs) were stimulated starting with peptide pools and subsequently with potentially reactive single peptides. In vitro T-cell stimulation resulted in the direct identification of three canonical and one cryptic HLA-A*03-restricted immunogenic peptides as well as five canonical and one cryptic HLA-B*15-restricted immunogenic peptide, with a specific IFNγ+/CD8+ T cell response of ≥ 0.02%. Highest T-cell responses were identified against two HLA-A*03-restricted and three HLA-B*15-restricted canonical peptides with up to 3.42% of IFNγ+/CD8+ T cells in patients 180 days post alloSCT. In conclusion, we identified specific T-cell responses against eight canonical and two cryptic HLA-A*03:01- and HLA-B*15:01-restricted peptides in healthy individuals and post-transplanted patients and which were classified as immunogenic. Of these, six peptides are novel HCMV-derived, immunogenic peptides according to the UniProt database, broadening the spectrum of immunogenic HCMV-derived peptides for personalized immune monitoring and vaccine development.
2024-06-16 | PXD043022 | Pride
Project description:Human cytomegalovirus (HCMV) is a widespread virus and can establish life-long latent infection in large populations. In order to establish persistent and latent infection in healthy individuals, HCMV encodes a large array of proteins that can modulate different components and pathways of host cells. It has been reported that pUL138 encoded by UL133-UL138 polycistronic locus promotes a latent infection in primary CD34+ HPCs infected in vitro. In this study, a recombinant HCMV, namely HanUL138del, was constructed by deleting the UL138 locus of Han, a clinic HCMV strain. Then a comparative quantitative proteomic analysis of Han and HanUL138del infected MRC5 cells was performed, aiming to study the effect of pUL138 on host cell in the context of HCMV infection. Our result indicated that at the early phase of HCMV infection, innate immune response was differentially activated, while at late phase of HCMV infection, multiple host proteins were differentially expressed, between Han or HanUL138del infected cells.
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