Protein kinase PKR catalytic activity is required for the PKR-dependent activation of mitogen-activated protein kinases and amplification of interferon beta induction following virus infection

The protein kinase regulated by RNA (PKR) enhances both activation of mitogen-activated protein kinases and the induction of interferon beta (IFN-beta) by measles virus defective in C-protein expression (Ck). Here we used complementation of human cell lines stably deficient in PKR (PKRkd) to probe the basis of these PKR-mediated responses. We found that PKRkd HeLa and amnion LI cell lines were defective for virus-mediated activation of IFN induction signaling components compared to PKR-sufficient control cells. Complementation of PKRkd cells with wildtype PKR, but not with PKR mutants defective in either catalytic activity or dsRNA-binding activity, restored JNK, p38 and ATF-2 phosphorylation and enhanced IFNI?, induction following infection. By contrast to mammalian PKR, the Z-DNA binding domain-containing fish homologue of PKR, PKZ, lacked the capacity to enhance Ck virus-mediated IFN-beta induction. Furthermore, inhibition of virus growth was observed with C-ko-infected PKRkd cells complemented with PKR but not with PKZ. (C) 2012 Elsevier Inc. All rights reserved.