Alphaviruses induce apoptosis in Bcl-2-overexpressing cells: evidence for a caspase-mediated, proteolytic

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D Grandgirard1, E Studer, L Monney

  • 1Institute of Medical Microbiology, University of Berne, Friedbuehlstrasse 51, CH-3010 Berne, Switzerland.

The EMBO Journal
|April 18, 1998
PubMed

Insights

Alphaviruses can overcome Bcl-2

Area of Science:

  • Molecular Biology
  • Virology
  • Cell Death Research

Background:

  • Bcl-2 protein is known to inhibit apoptosis, a process crucial for clearing viral infections.
  • It was hypothesized that Bcl-2 prevents viral infections by blocking caspase-3 activation.

Purpose of the Study:

  • To investigate whether Bcl-2 overexpression prevents apoptosis during alphavirus infection.
  • To determine the mechanism by which alphaviruses might evade Bcl-2-mediated cell death protection.

Main Methods:

  • Overexpression of functional Bcl-2 in three cell types.
  • Infection with Semliki Forest and Sindbis alphaviruses.
  • Analysis of caspase-3 activation and apoptosis.
  • Investigation of Bcl-2 cleavage using antibody epitope mapping.
  • Use of caspase inhibitor Z-VAD and a Bcl-2 mutant.

Main Results:

  • Cells overexpressing Bcl-2 still underwent apoptosis and caspase-3 activation upon alphavirus infection.
  • Bcl-2 was cleaved by caspases, inactivating its death-protective BH4 domain.
  • Caspase inhibition or a cleavage-resistant Bcl-2 mutant restored apoptosis resistance.

Conclusions:

  • Alphaviruses actively induce caspase-mediated cleavage and inactivation of Bcl-2.
  • This viral strategy allows evasion of Bcl-2-mediated apoptosis, promoting persistent infection.

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