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Protein kinase R contributes to immunity against specific viruses by regulating interferon mRNA integrity

Oliver Schulz1, Andreas Pichlmair, Jan Rehwinkel

  • 1Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK.

Cell Host & Microbe
|May 19, 2010
PubMed

Insights

The double-stranded RNA-binding protein kinase R (PKR) is crucial for interferon-alpha/beta production against certain RNA viruses by maintaining interferon mRNA stability. This finding clarifies PKR's role in innate immunity beyond RIG-I and MDA5.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Interferon-alpha/beta (IFN-alpha/beta) induction is vital for antiviral defense.
  • Cytosolic RNA sensors RIG-I and MDA5 are primary inducers of IFN-alpha/beta.
  • The role of double-stranded RNA-binding protein kinase R (PKR) in this process remains incompletely understood.

Purpose of the Study:

  • To elucidate the specific contribution and mechanism of PKR in IFN-alpha/beta production against RNA viruses.
  • To determine if PKR acts redundantly or nonredundantly with other known RNA sensors.

Main Methods:

  • Utilized cell lines with nonfunctional or reduced PKR levels.
  • Assessed IFN-alpha/beta protein and mRNA production in response to various RNA viruses.
  • Analyzed the integrity of IFN-alpha/beta mRNA, specifically its poly(A) tail.

Main Results:

  • PKR is essential for IFN-alpha/beta production against encephalomyocarditis, Theiler's murine encephalomyelitis, and Semliki Forest viruses, but not influenza or Sendai virus.
  • IFN-alpha/beta mRNA induction occurred normally in PKR-deficient cells, but a significant portion lacked poly(A) tails.
  • PKR plays a nonredundant role in the stability of IFN-alpha/beta mRNA.

Conclusions:

  • PKR is a critical regulator of IFN-alpha/beta production for a subset of RNA viruses.
  • PKR's mechanism involves maintaining the stability of IFN-alpha/beta mRNA, impacting its poly(A) tail.
  • This highlights a distinct pathway for innate immune response mediated by PKR.

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