Figures & data
Figure 1. Role of PKR in IFN-β induction and possible regulation of IFN-β mRNA integrity. Several stimuli such as viral origin dsRNA, pathogen ligands and cytokines (e.g., TNF-α) activate the proteinkinase R (PKR). An induced PKR phosphorylates the eukaryotic translation initiation factor 2 (eIF2-α) leading to its inactivation, thereby suppressing protein synthesis. PKR also activates the IKKα/β/γ-complex, which induces the ubiquitination and proteasomal degradation of inhibitor of NFκB (IκB), resulting in the liberation of active NFκB dimers [RelA/p65 and NFκB1 or 2 (p50/p52)]. Translocation of NFκB into the nucleus leads to the transcription of several genes, including IFN-β to limit viral replication. Upon the infection of MDA5-dependent viruses such as encephalomyocarditis virus (ECMV) and Semliki Forest virus (SFV), PKR also regulates the integrity of IFN-β mRNA by establishing or maintaining its poly(A) tail. It is also possible that PKR positively regulates IFN transcript stability by interacting with destabilizing elements in the mRNA, such as AU-rich elements or coding region instability determinant (CRID). Alternatively, PKR might counteract virus-encoded factors that destabilize IFN-β mRNA to suppress the host antiviral IFN response. P indicates phosphorylation, Ub indicates ubiquitination, and dotted lines indicate indirect action of PKR.
![Figure 1. Role of PKR in IFN-β induction and possible regulation of IFN-β mRNA integrity. Several stimuli such as viral origin dsRNA, pathogen ligands and cytokines (e.g., TNF-α) activate the proteinkinase R (PKR). An induced PKR phosphorylates the eukaryotic translation initiation factor 2 (eIF2-α) leading to its inactivation, thereby suppressing protein synthesis. PKR also activates the IKKα/β/γ-complex, which induces the ubiquitination and proteasomal degradation of inhibitor of NFκB (IκB), resulting in the liberation of active NFκB dimers [RelA/p65 and NFκB1 or 2 (p50/p52)]. Translocation of NFκB into the nucleus leads to the transcription of several genes, including IFN-β to limit viral replication. Upon the infection of MDA5-dependent viruses such as encephalomyocarditis virus (ECMV) and Semliki Forest virus (SFV), PKR also regulates the integrity of IFN-β mRNA by establishing or maintaining its poly(A) tail. It is also possible that PKR positively regulates IFN transcript stability by interacting with destabilizing elements in the mRNA, such as AU-rich elements or coding region instability determinant (CRID). Alternatively, PKR might counteract virus-encoded factors that destabilize IFN-β mRNA to suppress the host antiviral IFN response. P indicates phosphorylation, Ub indicates ubiquitination, and dotted lines indicate indirect action of PKR.](/cms/asset/3f166193-c9e6-4f93-bc3d-3d4766e156a7/kvir_a_10923134_f0001.gif)