Essential role for the dsRNA-dependent protein kinase PKR in innate immunity to viral infection

S Balachandran1, P C Roberts, L E Brown

  • 1Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 33136, USA.

Immunity
|August 10, 2000
PubMed

Insights

The protein kinase PKR is crucial for innate immunity against viruses. Mice lacking PKR show increased susceptibility to viral infections, highlighting its early host defense role.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • The double-stranded RNA-dependent protein kinase PKR is implicated in the interferon (IFN) response to viral infections.
  • Its precise role in early host defense against common viruses is not fully elucidated.

Purpose of the Study:

  • To investigate the role of PKR in innate immunity against viral infections.
  • To determine the mechanisms by which PKR mediates antiviral defense.

Main Methods:

  • Utilized a mouse model lacking the PKR gene.
  • Assessed susceptibility to intranasal infection with vesicular stomatitis virus and influenza virus.
  • Investigated viral mRNA translation inhibition and autocrine IFN production in PKR-deficient cells.

Main Results:

  • Mice lacking PKR exhibited lethal susceptibility to vesicular stomatitis virus and increased susceptibility to influenza virus.
  • PKR was found to inhibit viral mRNA translation via eIF2alpha phosphorylation.
  • PKR also promoted autocrine IFN production and established an antiviral state.

Conclusions:

  • PKR is an essential component of innate immunity, acting early in host defense.
  • PKR prevents viral replication by inhibiting translation and promoting IFN production.
  • These findings underscore PKR's critical role before adaptive immunity is engaged.

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