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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
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Independent regulation of reovirus membrane penetration and apoptosis by the mu1 phi domain

Pranav Danthi1, Caroline M Coffey, John S L Parker

  • 1Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA. pdanthi@indiana.edu

Plos Pathogens
|December 30, 2008
PubMed

Insights

The reovirus mu1 protein

Area of Science:

  • Virology
  • Cell Biology
  • Neuroscience

Background:

  • Apoptosis is crucial in reovirus encephalitis pathogenesis.
  • Reovirus outer-capsid protein mu1 regulates apoptosis during infection.
  • The mu1 phi domain is sufficient to trigger cell death.

Purpose of the Study:

  • To assess the mu1 phi domain's role in reovirus-induced apoptosis.
  • To generate and analyze phi mutant reoviruses.
  • To investigate the relationship between membrane penetration and apoptosis.

Main Methods:

  • Reverse genetics used to create phi mutant reoviruses.
  • Analysis of viral membrane penetration efficiency.
  • Assessment of apoptosis induction and neurovirulence in mice.

Main Results:

  • Mutations in the phi domain reduce reovirus membrane penetration.
  • The phi domain influences apoptotic potential independently of membrane penetration.
  • Apoptosis-defective phi mutant viruses show reduced neurovirulence.

Conclusions:

  • The mu1 phi domain is a key regulator of reovirus-induced apoptosis.
  • The phi domain initiates apoptosis after viral entry into the cytosol.
  • This finding highlights the role of mu1 in reovirus pathogenesis and disease.

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