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Review
. 2013 Jan 1;4(1):85-9.
doi: 10.4161/viru.23134.

The multiple faces of proteinkinase R in antiviral defense

Muhammad Munir  1 , Mikael Berg
Affiliations
Review

The multiple faces of proteinkinase R in antiviral defense

Muhammad Munir et al. Virulence. .

Abstract

Various pattern recognition receptors (PRRs) have been implicated in the detection of viral RNA and subsequent interferon (IFN) gene expression, including the double-stranded RNA-dependent proteinkinase R (PKR). Now, a novel role of PKR has been unveiled, as it was shown that, upon the infection with certain viruses, PKR is crucial for the integrity of newly synthesized IFN mRNA, thereby generating an optimal host antiviral immune response. There is a need of future studies to investigate additional roles of PKR in innate immunity and the molecular understanding of this novel function of PKR.

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Figures

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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.
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