Viral Infection Dispensable PKR

Double-stranded RNA (dsRNA) is detected by cells and triggers several different cellular responses. These pathways are important for controlling viral infections in the host and include stimulation of apoptosis to prevent spread of the virus, inhibition of protein synthesis to prevent viral replication, and induction of antiviral interferons and cytokines to stimulate the immune system (which requires suppression of apoptosis). Although protein kinase R (PKR) has been implicated in each of the dsRNA-triggered processes, Iordanov et al. found that the stimulation of the anti-apoptotic nuclear factor B (NF-B) pathway and the production of β-interferon, tumor necrosis factor-α, and interleukin-6 did not depend on PKR. Comparison of the phosphorylation and degradation of IBs (inhibitors of NF-B), nuclear translocation of NF-B, and DNA-binding by NF-B in wild-type and PKR-deficient mouse embryo fibroblasts in response to dsRNA showed that NF-B activation proceeded normally in wild-type and PKR-deficient cells. Stimulation of cytokines and interferons occurred in both the wild-type and PKR mutant cells. The authors propose that the anti-apoptotic responses triggered by dsRNA are controlled by a second sensor that is independent of PKR.

Iordanov, M.S., Wong, J., Bell, J.C., and Magun, B.E. (2000) Activation of NF-B by double-stranded RNA (dsRNA) in the absence of protein kinase R and RNase L demonstrates the existence of two separate dsRNA-triggered antiviral programs. Mol. Cell. Biol. 21: 61-72. [Abstract] [Full Text]