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.
Highlights
Antiviral innate immunity serves as a primary barrier to control viral infection in both immune and non-immune cells before the development of sophisticated adaptive immunity
We investigated the global transcriptome changes in response to viral infection in non-immune cells
We profiled the transcriptome changes of mouse embryonic fibroblast (MEFs) in response to viral mimic stimulation
Summary
Antiviral innate immunity serves as a primary barrier to control viral infection in both immune and non-immune cells before the development of sophisticated adaptive immunity. Toll-like receptors (TLRs) 3, 7, 8, and 9 are a group of pattern recognition receptors (PRRs) detecting early viral infection events in endosome [1]. Cytosolic DNA sensors such as cGAS, DAI and AIM2 are responsible for the detection of viral dsDNA [4]. The activation of these nucleic acids sensors recruits and activates different adaptors for signal transduction. The signal transduction from the activation of TLRs or RLRs eventually activates the protein kinase TBK1, which phosphorylates and activates transcription factors IRF3 and IRF7 to promote the production of type I interferons [7]. The secretion of type I interferons such as IFN-α and IFN-β, acts in an autocrine or paracrine manner to stimulate the expression of interferon-stimulated genes (ISGs) which exhibit anti-proliferative and antiviral effects [8]
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