Essential role for the dsRNA-dependent protein kinase PKR in innate immunity to viral infection

The double-stranded (ds) RNA-dependent protein kinase PKR is considered to play an important role in interferon's (IFN's) response to viral infection. Here, we demonstrate that mice lacking PKR are predisposed to lethal intra nasal infection by the usually innocuous vesicular stomatitis virus, and al so display increased susceptibility to influenza virus infection. Our data indicate that in normal cells, PKR primarily prevents virus replication by inhibiting the translation of viral mRNAs through phosphorylation of elF2 a lpha, while concomitantly assisting in the production of autocrine IFN and the establishment of an antiviral state. These results show that PKR is an essential component of innate immunity that acts early in host defense prio r to the onset of IFN counteraction and the acquired immune response.