Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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A comparison of gene expression between human dermal fibroblasts and neurons infected by varicella zoster virus

ABSTRACT: The cellular transcriptomes of VZV-infected fibroblasts and T-lymphocytes have been reported, but not that of human neurons. In order to determine the transcriptional response of human neurons to VZV infection, we generated 95%-pure populations of neurons from hESC, infected them with recombinant GFP-expressing cell-free VZV, and compared their transcriptome to that of human foreskin fibroblasts infected in parallel, using Agilent microarrays. Applying a twofold-change as the cutoff (p-value<0.05), we observed that transcription of 1654 fibroblast and 340 neuronal genes were upregulated, and 955 fibroblast and 38 neuronal genes were downregulated by VZV infection. 223 of these infection-regulated genes were unique to neurons. Gene ontology enrichment analysis revealed several clusters of genes regulated by VZV in neurons and fibroblasts differed. For example, neurons did not show upregulation of innate immune responses, NF-kappaB, response to stress and DNA repair clusters, in contrast to fibroblasts that upregulated these groups. This is the first study of the response of genetically normal human neurons to viral infection. Two-condition experiment, VZV-GFP23- fibroblast cells vs. fibroblast cells, and VZV-GFP23- neuron cells vs. neuron cells. Data from two biological replicates and two technical replicates were used for each condition.

ORGANISM(S): Homo sapiens

SUBMITTER: Hiba Waldman Ben-Asher

PROVIDER: E-GEOD-54385 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Cellular transcriptome analysis reveals differential expression of pro- and antiapoptosis genes by varicella-zoster virus-infected neurons and fibroblasts.

Markus Amos A Waldman Ben-Asher Hiba H Kinchington Paul R PR Goldstein Ronald S RS

Journal of virology 20140416 13

Transcriptional changes following varicella-zoster virus (VZV) infection of cultured human neurons derived from embryonic stem cells were compared to those in VZV-infected human foreskin fibroblasts. Transcription of 340 neuronal genes significantly altered by VZV infection included 223 transcript changes unique to neurons. Strikingly, genes inhibiting apoptosis were upregulated in neurons, while proapoptotic gene transcription was increased in fibroblasts. These data are a basis for discovery o ...[more]

PMID: 24741086

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Project description:Differentiated NT2 cells are a potentially useful model system to study herpes simples virus (HSV) replication in human neurons. These cells can be irreversibly differentiated into NT-neurons in the presence of retinoic acid and non-dividing cultures NT-neurons can be maintained for up to several months without retinoic acid. HSV is capable of infecting and replicating in differentiated NT-neurons and thus differentiated NT-neurons provide a ready source of human post-mitotic cells which can be useful to study certain aspects of the interaction of HSV and the neuron. Microarray analysis was used to examine how HSV-1 infection modulates cellular transcription in human NT-neurons, focusing on changes that take place during the first 24 hours following infection and compared to changes resulting from infection with inactivated virus. In addition, the transcriptional changes resulting from virus infection of neurons were compared to those observed in primary human fibroblasts. At early times after HSV infection a small number of cellular transcripts in NT-Neurons appear to be increased in abundance. Most of these transcripts that are up-regulated after infection are not unique to neuronal cells, and possibly represent a common cellular response to HSV infection. A few transcripts were not detected in infected human fibroblasts and may represent part of a transcriptional profile specific to this type of human neuronal cell. In contrast to the situation at early times after infection, analysis of cellular transcripts in NT-neurons at late times after infection is complicated by the overall profound decrease in cellular transcription. Thus, microarray analysis appeared to be most useful as a screening method for transcription changes following infection at early times after virus infection of NT-neurons. Two-condition experiment, HSV-1 infected versus uninfected fibroblasts, 3 independent biological replicate sets (uninfected/infected) in dual channel array setup (Cy3/Cy5).

Project description:During primary infection, varicella-zoster virus (VZV) is spread via lymphocytes to skin, where it induces a rash and establishes latency in sensory ganglia. A live, attenuated varicella vaccine (vOka) was generated by using the VZV Oka strain (pOka), but the molecular basis for vOka attenuation remains unknown. Little is known concerning the effects of wild-type or attenuated VZV on cellular gene regulation in the host cells that are critical for pathogenesis. In this study, transcriptional profiles of primary human T cells and fibroblasts infected with VZV in cell culture were determined by using 40,000-spot human cDNA microarrays. Cellular gene transcription in human skin xenografts in SCID mice that were infected with VZV in vivo was also evaluated. The profiles of cellular gene transcripts that were induced or inhibited in infected human foreskin fibroblasts (HFFs), T cells, and skin in response to pOka and vOka infection were similar. However, significant alterations in cellular gene regulation were observed among the three differentiated human cell types that were examined, suggesting specific differences in the biological consequences of VZV infection related to the target cell. Changes in cellular gene transcription detected by microarray analysis were confirmed for selected genes by quantitative real-time reverse transcription-PCR analysis of VZV-infected cells. Interestingly, the transcription of caspase 8 was found to be decreased in infected T cells but not in HFFs or skin, which may signify a tissue-specific antiapoptosis mechanism. The use of microarrays to demonstrate differences in effects on host cell genes in primary, biologically relevant cell types provides background information for experiments to link these various response phenotypes with mechanisms of VZV pathogenesis that are important for the natural course of human infection. A pathogenicity experiment design type is where an infective agent such as a bacterium, virus, protozoan, fungus etc. infects a host organism(s) and the infective agent is assayed. Computed

Dataset Information

A comparison of gene expression between human dermal fibroblasts and neurons infected by varicella zoster virus

Publications

Cellular transcriptome analysis reveals differential expression of pro- and antiapoptosis genes by varicella-zoster virus-infected neurons and fibroblasts.

Similar Datasets

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