Protein Kinase R Contributes to Immunity against Specific Viruses by Regulating Interferon mRNA Integrity.

Summary: Cytosolic viral RNA recognition by the helicases RIG-I and MDA5 is considered the major pathway for IFN-α/β induction in response to RNA viruses. However, other cytoplasmic RNA sensors, including the double-stranded RNA-binding protein kinase R (PKR), have been implicated in IFN-α/β production, although their relative contribution and mechanism have been unclear. Using cells expressing nonfunctional PKR or reduced levels of kinase, we show that PKR is required for production of IFN-α/β proteins in response to a subset of RNA viruses including encephalomyocarditis, Theiler''s murine encephalomyelitis, and Semliki Forest virus, but not influenza or Sendai virus. Surprisingly, although IFN-α/β mRNA induction is largely normal in PKR-deficient cells, much of that mRNA lacks the poly(A) tail, indicating that its integrity is compromised. Our results suggest that PKR plays a nonredundant role in IFN-α/β production in response to some but not all viruses, in part by regulating IFN-α/β mRNA stability. [Copyright &y& Elsevier]