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.
Activation of EGFR on monocytes is required for human cytomegalovirus entry and mediates cellular motility.
Specimen part
View SamplesHuman cytomegalovirus induces a pro-inflammatory monocyte following infection and we have evidence that NF-B 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-B- 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.
Transcriptome analysis of NF-kappaB- and phosphatidylinositol 3-kinase-regulated genes in human cytomegalovirus-infected monocytes.
Specimen part
View SamplesHuman 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.
Transcriptome analysis reveals human cytomegalovirus reprograms monocyte differentiation toward an M1 macrophage.
Specimen part
View SamplesWe have established that human cytomegalovirus (HCMV) infection modulates the biology of target primary blood monocytes, allowing HCMV to use monocytes as vehicles for its systemic spread. HCMV infection of monocytes results in rapid induction of PI(3)K and NF-B activity. Integrins, which are upstream of the PI(3)K and NF-B pathways, were shown to be involved in HCMV binding to and entry into fibroblasts, suggesting that receptor-ligand-mediated signaling following viral binding to integrins on monocytes could trigger the functional changes seen in infected monocytes. We now show that integrin engagement and the activation of the integrin/Src-signaling pathway is essential for the induction of HCMV-infected monocyte motility. To investigate how integrin engagement by HCMV triggers monocyte motility, we examined the infected monocyte transcriptome and found that the integrin/Src-signaling pathway regulates the expression of paxillin, which is an important signal transducer in the regulation of actin rearrangement during cell adhesion and movement. Functionally, we observed that paxillin is activated via the integrin/Src-signaling pathway and is required for monocyte motility. Because motility is intimately connected to cellular cytoskeletal organization, a process that is also important in viral entry, we investigated the role paxillin regulation plays in the process of viral entry of monocytes. New results confirmed that HCMV`s ability to enter target monocytes is significantly inhibited in cells deficient in paxillin expression or that had their integrin/Src/paxillin signaling pathway blocked. From our data, HCMV-cell interactions emerge as an essential trigger for the cellular changes that allow for HCMV entry and hematogenous dissemination.
No associated publication
Specimen part
View SamplesHuman 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.
PI3K-dependent upregulation of Mcl-1 by human cytomegalovirus is mediated by epidermal growth factor receptor and inhibits apoptosis in short-lived monocytes.
Specimen part
View Samplesthe molecular mechanisms for the biphasic effect of alcohol are not fully understood. The goal of the study is to identify genes that are differentially expressed following alcohol exposure of 50mM and 100mM ethanol for 24 hours.
Ethanol upregulates glucocorticoid-induced leucine zipper expression and modulates cellular inflammatory responses in lung epithelial cells.
No sample metadata fields
View SamplesWe have identified genes that are differentially expressed between the bladders of UPII-SV40Tag mice and their age-matched wild-type littermates at 3, 6, 20, and 30 weeks of age. These are ages that correspond to premalignant, carcinoma in situ, and early-stage and later stage invasive UCC, respectively
Identification of genes correlated with early-stage bladder cancer progression.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Regulation of Virus-Associated Lymphoma Growth and Gene Expression by Bacterial Quorum-Sensing Molecules.
Cell line, Treatment
View SamplesGenes upregulated in stroke infiltrating stem cells were compared against the parent non-infiltrated mouse stem cell line derived from immortomouseTM.
No associated publication
No sample metadata fields
View SamplesThe Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma (KS), the most common HIV/AIDS-associated tumor worldwide. Involvement of the oral cavity portends a poor prognosis for patients with KS, but mechanisms for KSHV regulation of the oral tumor microenvironment are largely unknown. Infiltrating fibroblasts are found with KS lesions, and KSHV establishes latent infection within human primary fibroblasts in vitro, but contributions for KSHV-infected fibroblasts to the KS microenvironment have not been previously characterized. In the present study, we used Illumina microarray to detect the global gene profile altered in KSHV-infected primary human fibroblasts (PDLF and HGF) isolated from the oral cavity.
Transcriptomic analysis of KSHV-infected primary oral fibroblasts: The role of interferon-induced genes in the latency of oncogenic virus.
Specimen part
View Samples