P58(IPK), a plant ortholog of double-stranded RNA-dependent protein kinase PKR inhibitor, functions in viral pathogenesis

Dev Cell. 2003 May;4(5):651-61. doi: 10.1016/s1534-5807(03)00125-4.

Abstract

P58(IPK) is a cellular inhibitor of the mammalian double-stranded RNA-activated protein kinase (PKR). Here we provide evidence for the existence of its homolog in plants and its role in viral infection at the organism level. Viral infection of P58(IPK)-silenced Nicotiana benthamiana and Arabidopsis knockouts leads to host death. This host cell death is associated with phosphorylation of the alpha subunit of eukaryotic translation initiation factor (eIF-2alpha). Loss of P58(IPK) leads to reduced virus titer, suggesting that wild-type P58(IPK) protein plays an important role in viral pathogenesis. Although our complementation results using mammalian P58(IPK) suggest conservation of the P58(IPK) pathway in plants and animals, its biological significance seems to be different in these two systems. In animals, P58(IPK) is recruited by the influenza virus to limit PKR-mediated innate antiviral response. In plants, P58(IPK) is required by viruses for virulence and therefore functions as a susceptibility factor.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Arabidopsis / growth & development
  • Arabidopsis / virology
  • Eukaryotic Initiation Factor-2 / genetics
  • Eukaryotic Initiation Factor-2 / metabolism
  • Gene Deletion
  • Gene Expression Regulation, Plant
  • Gene Silencing
  • HSP40 Heat-Shock Proteins
  • Mice
  • Molecular Sequence Data
  • Nicotiana / growth & development
  • Nicotiana / virology
  • Phosphorylation
  • Plant Proteins / chemistry
  • Plant Proteins / genetics
  • Plant Proteins / metabolism*
  • Plant Viruses / pathogenicity*
  • Plant Viruses / physiology
  • Protein Binding
  • Protein Kinase Inhibitors
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Two-Hybrid System Techniques
  • eIF-2 Kinase / metabolism

Substances

  • Dnajc3 protein, mouse
  • Eukaryotic Initiation Factor-2
  • HSP40 Heat-Shock Proteins
  • P58IPK protein, plant
  • Plant Proteins
  • Protein Kinase Inhibitors
  • RNA, Messenger
  • Repressor Proteins
  • eIF-2 Kinase