Protein Kinase R

    Cards (21)

    • Interferon gamma
      Upregulates the expression levels of the PKR protein
    • When the PKR pathway is activated
      Limits replication by an eIF2a-mediated block of translation
    • PKR requires a minimum of 33bp of perfect dsRNA for induction and around 80bp or more for optimal activation
    • EIF2a
      • Key part of ribosomal translation initiation
    • Viruses counteract PKR activity by using their own viral products or hijacking cellular proteins
    • PKR can act as a signal transducer in the IkB/NFkB pathway

      Plays a role in the control of cellular processes such as apoptosis, cell growth, differentiation, and response to cellular stress other than viral infection
    • Protein kinase R (PKR)

      • Serine-threonine kinase encoded by the EIF2AK2 gene in humans, plays a major role in central cellular processes such as mRNA translation, transcriptional control, regulation of apoptosis and proliferation
    • PKR PAMPs
      • dsRNA
      • Synthetic structures ds-RNA with single-stranded tails and 5'triphosphate
      • HIV-1 TAR RNA
      • Either complete or incomplete influenza virus vRNP
    • Active PKR phosphorylates its substrate eIF2a, resulting in a block of translation
    • Activation of PKR during viral infection
      Mediated by recognition of viral nucleic acid (dsRNA), inducing a structural rearrangement and bringing two PKR monomers into close proximity
    • Small amounts of PKR activation lead to the induction of type I interferons, resulting in the upregulation of interferon-stimulated genes, including PKR, creating a positive feedback loop
    • Contribution to antiviral immunity
      PKR-mediated block of translation impairs efficient viral reproduction and spread
    • One mechanism viruses use to evade PKR response is hiding or sequestering dsRNA molecules
    • Mechanisms of viruses evading immune response
      1. Hiding or Sequestering dsRNA molecules
      2. PKR Degradation
      3. Inhibition of PKR Dimerisation and Autophosphorylation
      4. Interacting viral proteins
      5. Acting downstream from eIf2a
    • Viral proteins acting downstream from eIf2a
      • NS4A protein from Dengue virus (DENV)
    • Viruses limiting dsRNA availability through degradation
      • Avian coronavirus
    • Inhibition of PKR Dimerisation and Autophosphorylation by viruses
      • Hantavirus
    • Interacting viral proteins inhibiting PKR kinase activation
      • E2 envelope protein of hepatitis C virus
      • K3L of VACV
    • PKR Degradation by viruses
      • Toscana virus (TOSV)
      • Rift valley fever virus (RVFV)
    • dsRNA sequestering viral proteins

      • MERS-CoV protein 4a
      • E3L protein of vaccinia virus (VACV)
      • NS1 Protein of Influenza
      • σ3 outer capsid protein of mammalian reovirus
    • Viruses evading immune response
      Many viruses evolved to counteract PKR activity by using their own viral products or by hijacking cellular proteins