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Viruses 2012, 4(11), 2598-2635; doi:10.3390/v4112598
Review

dsRNA-Dependent Protein Kinase PKR and its Role in Stress, Signaling and HCV Infection

 and *
Received: 4 September 2012; in revised form: 18 October 2012 / Accepted: 22 October 2012 / Published: 29 October 2012
(This article belongs to the Special Issue Hepatitis C Pathology)
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Abstract: The double-stranded RNA-dependent protein kinase PKR plays multiple roles in cells, in response to different stress situations. As a member of the interferon (IFN)‑Stimulated Genes, PKR was initially recognized as an actor in the antiviral action of IFN, due to its ability to control translation, through phosphorylation, of the alpha subunit of eukaryotic initiation factor 2 (eIF2a). As such, PKR participates in the generation of stress granules, or autophagy and a number of viruses have designed strategies to inhibit its action. However, PKR deficient mice resist most viral infections, indicating that PKR may play other roles in the cell other than just acting as an antiviral agent. Indeed, PKR regulates several signaling pathways, either as an adapter protein and/or using its kinase activity. Here we review the role of PKR as an eIF2a kinase, its participation in the regulation of the NF-kB, p38MAPK and insulin pathways, and we focus on its role during infection with the hepatitis C virus (HCV). PKR binds the HCV IRES RNA, cooperates with some functions of the HCV core protein and may represent a target for NS5A or E2. Novel data points out for a role of PKR as a pro-HCV agent, both as an adapter protein and as an eIF2a-kinase, and in cooperation with the di-ubiquitin-like protein ISG15. Developing pharmaceutical inhibitors of PKR may help in resolving some viral infections as well as stress-related damages.
Keywords: PKR; dsRNA; IFN; eIF2a; PRR; HCV; MAVS; ISG15; RIG-I PKR; dsRNA; IFN; eIF2a; PRR; HCV; MAVS; ISG15; RIG-I
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Dabo, S.; Meurs, E.F. dsRNA-Dependent Protein Kinase PKR and its Role in Stress, Signaling and HCV Infection. Viruses 2012, 4, 2598-2635.

AMA Style

Dabo S, Meurs EF. dsRNA-Dependent Protein Kinase PKR and its Role in Stress, Signaling and HCV Infection. Viruses. 2012; 4(11):2598-2635.

Chicago/Turabian Style

Dabo, Stéphanie; Meurs, Eliane F. 2012. "dsRNA-Dependent Protein Kinase PKR and its Role in Stress, Signaling and HCV Infection." Viruses 4, no. 11: 2598-2635.



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