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

Abstract

Summary Cytosolic recognition of viral RNA by the RNA helicases RIG-I and MDA5 is thought to be the major pathway for IFN-α/β induction by RNA viruses. However, other cytoplasmic RNA sensors have historically been implicated in IFN-α/β production. Here we have re-examined the role of the double-stranded RNA binding protein kinase R (PKR). Using cells expressing non-functional 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, induction of IFN-α/β mRNA is largely normal in PKR-deficient cells. However, much of that mRNA lacks the poly A tail, indicating that its integrity is compromised. Our results suggest that PKR plays a non-redundant role in IFN-α/β production in response to some but not all viruses, in part by regulating IFN-α/β mRNA stability.