Tipping the balance: antagonism of PKR kinase and ADAR1 deaminase functions by virus gene products

J Interferon Cytokine Res. 2009 Sep;29(9):477-87. doi: 10.1089/jir.2009.0065.


The protein kinase regulated by RNA (PKR) and the adenosine deaminase acting on RNA (ADAR1) are interferon-inducible enzymes that play important roles in biologic processes including the antiviral actions of interferons, signal transduction, and apoptosis. PKR catalyzes the RNA-dependent phosphorylation of protein synthesis initiation factor eIF-2 alpha, thereby leading to altered translational patterns in interferon-treated and virus-infected cells. PKR also modulates signal transduction responses, including the induction of interferon. ADAR1 catalyzes the deamination of adenosine (A) to generate inosine (I) in RNAs with double-stranded character. Because I is recognized as G instead of A, A-to-I editing by ADAR1 can lead to genetic recoding and altered RNA structures. The importance of PKR and ADAR1 in innate antiviral immunity is illustrated by a number of viruses that encode either RNA or protein viral gene products that antagonize PKR and ADAR1 enzymatic activity, localization, or stability.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adenosine Deaminase / genetics
  • Adenosine Deaminase / immunology
  • Adenosine Deaminase / metabolism*
  • Animals
  • Antiviral Agents / immunology
  • Antiviral Agents / metabolism
  • Apoptosis
  • Enzyme Inhibitors / immunology
  • Enzyme Inhibitors / metabolism
  • Eukaryotic Initiation Factor-2 / genetics
  • Eukaryotic Initiation Factor-2 / immunology
  • Eukaryotic Initiation Factor-2 / metabolism
  • Humans
  • Immunity, Innate
  • Interferons / immunology
  • RNA Editing
  • RNA Virus Infections / enzymology*
  • RNA Virus Infections / genetics*
  • RNA Virus Infections / immunology
  • RNA Viruses / pathogenicity
  • RNA Viruses / physiology*
  • RNA-Binding Proteins
  • Signal Transduction
  • Viral Proteins / immunology
  • Viral Proteins / metabolism
  • eIF-2 Kinase / genetics
  • eIF-2 Kinase / immunology
  • eIF-2 Kinase / metabolism*


  • Antiviral Agents
  • Enzyme Inhibitors
  • Eukaryotic Initiation Factor-2
  • RNA-Binding Proteins
  • Viral Proteins
  • Interferons
  • eIF-2 Kinase
  • ADARB1 protein, human
  • Adenosine Deaminase