Analysis of Global Transcriptome Change in Mouse Embryonic Fibroblasts After dsDNA and dsRNA Viral Mimic Stimulation

Xin Xie, Pu Ste Liu, Piergiorgio Percipalle

Research output: Contribution to journalArticle

Abstract

The activation of innate immunity by viral nucleic acids present in the cytoplasm plays an essential role in controlling viral infection in both immune and non-immune cells. The dsDNA and dsRNA viral mimics can stimulate the cytosolic nucleic acids sensors and activate the antiviral innate immunity. In this study, taking advantage of dsDNA and dsRNA viral mimics, we investigated the global transcriptome changes after the antiviral immunity activation in mouse embryonic fibroblasts. Results from our data identified a positive feedback up-regulation of sensors (e.g., Tlr2, Tlr3, Ddx58, cGAS), transducers (e.g., Traf2, Tbk1) and transcription factors (e.g., Irf7, Jun, Stat1, Stat2) in multiple pathways involved in detecting viral or microbial infections upon viral mimic stimulation. A group of genes involved in DNA damage response and DNA repair such as Parp9, Dtx3l, Rad52 were also up-regulated, implying the involvement of these genes in antiviral immunity. Molecular function analysis further showed that groups of helicase genes (e.g., Dhx58, Helz2), nuclease genes (e.g., Dnase1l3, Rsph10b), methyltransferase genes (e.g., histone methyltransferase Prdm9, Setdb2; RNA methyltransferase Mettl3, Mttl14), and protein ubiquitin-ligase genes (e.g., Trim genes and Rnf genes) were up-regulated upon antiviral immunity activation. In contrast, viral mimic stimulation down-regulated genes involved in a broad range of general biological processes (e.g., cell division, metabolism), cellular components (e.g., mitochondria and ribosome), and molecular functions (e.g., cell-cell adhesion, microtubule binding). In summary, our study provides valuable information about the global transcriptome changes upon antiviral immunity activation. The identification of novel groups of genes up-regulated upon antiviral immunity activation serves as useful resource for mining new antiviral sensors and effectors.

Original languageEnglish (US)
Number of pages1
JournalFrontiers in immunology
Volume10
DOIs
StatePublished - Jan 1 2019

Fingerprint

Gene Expression Profiling
Fibroblasts
Antiviral Agents
Genes
Immunity
Methyltransferases
Virus Diseases
Transcriptome
Innate Immunity
Nucleic Acids
tebufenozide
Biological Phenomena
Social Identification
Ubiquitin-Protein Ligases
Transducers
Ribosomes
Cell Adhesion
Microtubules
DNA Repair
Cell Division

Keywords

  • genome-wide analysis
  • innate immunity
  • mouse embryonic fibroblasts
  • transcriptional profiling
  • viral mimic stimulation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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title = "Analysis of Global Transcriptome Change in Mouse Embryonic Fibroblasts After dsDNA and dsRNA Viral Mimic Stimulation",
abstract = "The activation of innate immunity by viral nucleic acids present in the cytoplasm plays an essential role in controlling viral infection in both immune and non-immune cells. The dsDNA and dsRNA viral mimics can stimulate the cytosolic nucleic acids sensors and activate the antiviral innate immunity. In this study, taking advantage of dsDNA and dsRNA viral mimics, we investigated the global transcriptome changes after the antiviral immunity activation in mouse embryonic fibroblasts. Results from our data identified a positive feedback up-regulation of sensors (e.g., Tlr2, Tlr3, Ddx58, cGAS), transducers (e.g., Traf2, Tbk1) and transcription factors (e.g., Irf7, Jun, Stat1, Stat2) in multiple pathways involved in detecting viral or microbial infections upon viral mimic stimulation. A group of genes involved in DNA damage response and DNA repair such as Parp9, Dtx3l, Rad52 were also up-regulated, implying the involvement of these genes in antiviral immunity. Molecular function analysis further showed that groups of helicase genes (e.g., Dhx58, Helz2), nuclease genes (e.g., Dnase1l3, Rsph10b), methyltransferase genes (e.g., histone methyltransferase Prdm9, Setdb2; RNA methyltransferase Mettl3, Mttl14), and protein ubiquitin-ligase genes (e.g., Trim genes and Rnf genes) were up-regulated upon antiviral immunity activation. In contrast, viral mimic stimulation down-regulated genes involved in a broad range of general biological processes (e.g., cell division, metabolism), cellular components (e.g., mitochondria and ribosome), and molecular functions (e.g., cell-cell adhesion, microtubule binding). In summary, our study provides valuable information about the global transcriptome changes upon antiviral immunity activation. The identification of novel groups of genes up-regulated upon antiviral immunity activation serves as useful resource for mining new antiviral sensors and effectors.",
keywords = "genome-wide analysis, innate immunity, mouse embryonic fibroblasts, transcriptional profiling, viral mimic stimulation",
author = "Xin Xie and Liu, {Pu Ste} and Piergiorgio Percipalle",
year = "2019",
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doi = "10.3389/fimmu.2019.00836",
language = "English (US)",
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T1 - Analysis of Global Transcriptome Change in Mouse Embryonic Fibroblasts After dsDNA and dsRNA Viral Mimic Stimulation

AU - Xie, Xin

AU - Liu, Pu Ste

AU - Percipalle, Piergiorgio

PY - 2019/1/1

Y1 - 2019/1/1

N2 - The activation of innate immunity by viral nucleic acids present in the cytoplasm plays an essential role in controlling viral infection in both immune and non-immune cells. The dsDNA and dsRNA viral mimics can stimulate the cytosolic nucleic acids sensors and activate the antiviral innate immunity. In this study, taking advantage of dsDNA and dsRNA viral mimics, we investigated the global transcriptome changes after the antiviral immunity activation in mouse embryonic fibroblasts. Results from our data identified a positive feedback up-regulation of sensors (e.g., Tlr2, Tlr3, Ddx58, cGAS), transducers (e.g., Traf2, Tbk1) and transcription factors (e.g., Irf7, Jun, Stat1, Stat2) in multiple pathways involved in detecting viral or microbial infections upon viral mimic stimulation. A group of genes involved in DNA damage response and DNA repair such as Parp9, Dtx3l, Rad52 were also up-regulated, implying the involvement of these genes in antiviral immunity. Molecular function analysis further showed that groups of helicase genes (e.g., Dhx58, Helz2), nuclease genes (e.g., Dnase1l3, Rsph10b), methyltransferase genes (e.g., histone methyltransferase Prdm9, Setdb2; RNA methyltransferase Mettl3, Mttl14), and protein ubiquitin-ligase genes (e.g., Trim genes and Rnf genes) were up-regulated upon antiviral immunity activation. In contrast, viral mimic stimulation down-regulated genes involved in a broad range of general biological processes (e.g., cell division, metabolism), cellular components (e.g., mitochondria and ribosome), and molecular functions (e.g., cell-cell adhesion, microtubule binding). In summary, our study provides valuable information about the global transcriptome changes upon antiviral immunity activation. The identification of novel groups of genes up-regulated upon antiviral immunity activation serves as useful resource for mining new antiviral sensors and effectors.

AB - The activation of innate immunity by viral nucleic acids present in the cytoplasm plays an essential role in controlling viral infection in both immune and non-immune cells. The dsDNA and dsRNA viral mimics can stimulate the cytosolic nucleic acids sensors and activate the antiviral innate immunity. In this study, taking advantage of dsDNA and dsRNA viral mimics, we investigated the global transcriptome changes after the antiviral immunity activation in mouse embryonic fibroblasts. Results from our data identified a positive feedback up-regulation of sensors (e.g., Tlr2, Tlr3, Ddx58, cGAS), transducers (e.g., Traf2, Tbk1) and transcription factors (e.g., Irf7, Jun, Stat1, Stat2) in multiple pathways involved in detecting viral or microbial infections upon viral mimic stimulation. A group of genes involved in DNA damage response and DNA repair such as Parp9, Dtx3l, Rad52 were also up-regulated, implying the involvement of these genes in antiviral immunity. Molecular function analysis further showed that groups of helicase genes (e.g., Dhx58, Helz2), nuclease genes (e.g., Dnase1l3, Rsph10b), methyltransferase genes (e.g., histone methyltransferase Prdm9, Setdb2; RNA methyltransferase Mettl3, Mttl14), and protein ubiquitin-ligase genes (e.g., Trim genes and Rnf genes) were up-regulated upon antiviral immunity activation. In contrast, viral mimic stimulation down-regulated genes involved in a broad range of general biological processes (e.g., cell division, metabolism), cellular components (e.g., mitochondria and ribosome), and molecular functions (e.g., cell-cell adhesion, microtubule binding). In summary, our study provides valuable information about the global transcriptome changes upon antiviral immunity activation. The identification of novel groups of genes up-regulated upon antiviral immunity activation serves as useful resource for mining new antiviral sensors and effectors.

KW - genome-wide analysis

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KW - mouse embryonic fibroblasts

KW - transcriptional profiling

KW - viral mimic stimulation

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