The murine double-stranded RNA-dependent protein kinase PKR is required for resistance to vesicular stomatitis virus

D F Stojdl1, N Abraham, S Knowles

  • 1Ottawa Regional Cancer Centre Research Laboratories, Ottawa, Ontario K1H 8L6.

Journal of Virology
|September 23, 2000
PubMed

Insights

The double-stranded RNA-dependent protein kinase PKR is crucial for interferon-mediated antiviral defense against vesicular stomatitis virus (VSV). Mice lacking PKR are highly susceptible to VSV, highlighting PKR

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Interferon (IFN)-induced antiviral responses rely on various proteins, including protein kinase PKR.
  • PKR plays a role in cellular defense against viral infections.

Purpose of the Study:

  • To investigate the role of protein kinase PKR in the host defense against vesicular stomatitis virus (VSV).
  • To determine the importance of PKR in IFN-mediated protection against VSV infection.

Main Methods:

  • Utilized fibroblasts and mice genetically deficient in PKR (PKR(-/-)).
  • Infected PKR(-/-) and wild-type mice with VSV via intranasal instillation.
  • Assessed viral susceptibility, IFN-mediated protection, and pathology.

Main Results:

  • PKR(-/-) fibroblasts were more susceptible to VSV infection.
  • PKR(-/-) mice exhibited extreme susceptibility to intranasal VSV, succumbing rapidly.
  • alpha/beta-IFN failed to protect PKR(-/-) mice from VSV.
  • PKR(-/-) mice died from acute respiratory tract infection, not CNS pathology.

Conclusions:

  • PKR is a major component of IFN-mediated resistance to VSV.
  • The essentiality of PKR in antiviral defense is pathogen-specific.
  • PKR is critical for controlling VSV replication in the respiratory tract.

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