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Reovirus apoptosis and virulence are regulated by host cell membrane penetration efficiency

Pranav Danthi1, Takeshi Kobayashi, Geoffrey H Holm

  • 1Lamb Center for Pediatric Research, D7235 MCN, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

Journal of Virology
|October 26, 2007
PubMed

Insights

Reovirus encephalitis and myocarditis involve apoptosis, influenced by the mu1 protein

Area of Science:

  • Virology
  • Cellular Biology
  • Immunology

Background:

  • Apoptosis is crucial in reovirus-induced encephalitis and myocarditis.
  • Reovirus strains differ in apoptosis efficiency, linked to the M2 gene segment encoding the mu1 protein.
  • Viral disassembly within endosomes, not RNA synthesis, is required for reovirus-induced apoptosis.

Purpose of the Study:

  • To elucidate the mechanisms by which the reovirus mu1 protein induces apoptosis.
  • To investigate the role of mu1's membrane penetration activity in activating proapoptotic signaling pathways and reovirus pathogenesis.

Main Methods:

  • Generation of mu1 mutant viruses using reverse genetics.
  • Analysis of mutant viruses for membrane penetration, proapoptotic signaling activation (NF-kappaB, IRF-3), cell death induction, and encephalitis in mice.
  • Pharmacologic inhibition of reovirus replication to study apoptosis induction requirements.

Main Results:

  • Single amino acid substitutions in the mu1 delta region impaired membrane penetration.
  • These mutations reduced the activation of NF-kappaB and IRF-3, diminished apoptosis, and decreased reovirus virulence in mice.
  • Apoptosis induction by reovirus requires viral disassembly in endosomes, with mu1's membrane-penetrating function being key.

Conclusions:

  • The membrane penetration activity of the reovirus mu1 protein is critical for activating prodeath signaling pathways.
  • Mu1's role in membrane penetration is essential for reovirus pathogenesis, including encephalitis and myocarditis.
  • Targeting mu1's function could offer strategies for managing reovirus infections.

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