One defense against viral infection is provided by PKR, double-stranded RNA activated protein kinase. When PKR interacts with dsRNA found in cells during viral infection, PKR phosphorylates itself and cellular proteins including the translation factor elF2a and the transcription factor NF-kB. The repression of translation caused by phosphorylation of elF2a prevents cells from producing viral proteins and creating infectious viral particles. PKR phosphorylation of I-kB kinase activates NF-kB to induce transcription of inflammatory factors and stimulate an immune response that impedes viral infection. The PKR kinase is induced by interferon and some of the anti-viral activity of interferon may be mediated by PKR. Some viruses have evolved mechanisms to inactivate PKR to promote successful infection. Another substrate of PKR, the tumor suppressor p53, may be involved in potential PKR regulation of the cell cycle and apoptosis.
Contributor: Glenn Croston, PhD.
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