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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
08:32

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Published on: March 2, 2014

Alpha/beta interferons potentiate virus-induced apoptosis through activation of the FADD/Caspase-8 death signaling

S Balachandran1, P C Roberts, T Kipperman

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

Journal of Virology
|January 11, 2000
PubMed

Insights

Interferon (IFN) primes cells for apoptosis via PKR activation when infected with influenza virus. However, IFN also protects cells from other viruses by preventing replication without causing cell death.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Interferons (IFNs) are crucial for antiviral defense, inducing genes like PKR.
  • PKR (double-stranded RNA-dependent protein kinase) plays a role in cellular responses to viral infections.

Purpose of the Study:

  • To investigate the role of PKR in virus-induced apoptosis.
  • To elucidate the mechanisms by which IFN influences cellular responses to different viruses.

Main Methods:

  • Overexpression of functional and dominant-negative PKR in murine fibroblasts.
  • Induction of apoptosis using influenza virus, VSV, and Sindbis virus.
  • Analysis of death signaling pathways (FADD/caspase-8, caspase-9).
  • Treatment with IFN-alpha/beta.

Main Results:

  • PKR overexpression sensitized cells to influenza virus-induced apoptosis via FADD/caspase-8.
  • VSV and Sindbis virus induced cytolysis via caspase-9, independent of PKR-mediated apoptosis.
  • IFN-alpha/beta sensitized cells to dsRNA or influenza virus-induced apoptosis but protected against VSV/SNV replication.
  • IFN appears to prime cells for FADD-dependent apoptosis and inhibit viral replication through non-cytopathic mechanisms.

Conclusions:

  • PKR modulates apoptosis sensitivity during viral infections.
  • IFN exhibits dual roles: sensitizing to certain apoptotic pathways while protecting against others via non-cytopathic antiviral effects.

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