Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human HCMV-Infected monocytes

ABSTRACT: Human cytomegalovirus induces a pro-inflammatory monocyte following infection and we have evidence that NF-ÎºB 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-ÎºB- 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-ÎºB 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-ÎºB 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-ÎºB 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Andrew Yurochko

PROVIDER: E-GEOD-9601 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Transcriptome analysis of NF-kappaB- and phosphatidylinositol 3-kinase-regulated genes in human cytomegalovirus-infected monocytes.

Chan Gary G Bivins-Smith Elizabeth R ER Smith M Shane MS Yurochko Andrew D AD

Journal of virology 20071114 2

Human cytomegalovirus induces a proinflammatory monocyte following infection, and we have evidence that NF-kappaB and phosphatidylinositol 3-kinase [PI(3)K] are key mediators in this early activation. To begin to address how these signaling pathways are responsible for the rapid activation of infected monocytes, we examined the role that these pathways played in the transcriptome of infected monocytes. Global transcriptional profiling using cDNA microarrays revealed that a significant number of ...[more]

PMID: 18003728

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Project description:We 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-kB activity. Integrins, which are upstream of the PI(3)K and NF-kB 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. Monocytes were mock-infected, HCMV-infected, or pretreated with PP2 inhibitor prior to HCMV infection. There were three samples analyzed per individual replicate. Three replicates are included. comparative studies with a use of the specific Src kinase activity inhibitor

Dataset Information

Transcription profiling of human HCMV-Infected monocytes

Publications

Transcriptome analysis of NF-kappaB- and phosphatidylinositol 3-kinase-regulated genes in human cytomegalovirus-infected monocytes.

Similar Datasets

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