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Published on: October 21, 2012
Poliovirus 2A protease induces apoptotic cell death
D Goldstaub1, A Gradi, Z Bercovitch
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Molecular and Cellular Biology
|January 29, 2000
Summary
Poliovirus 2A protease expression in mammalian cells triggers apoptosis. This viral protease induces programmed cell death by cleaving translation factors and disrupting protein synthesis, leading to cell fragmentation and DNA damage.
Area of Science:
- Molecular Biology
- Virology
- Cell Biology
Background:
- Poliovirus 2A protease is a key viral enzyme involved in viral replication.
- Understanding the cellular targets and effects of viral proteases is crucial for comprehending viral pathogenesis.
Purpose of the Study:
- To investigate the effects of inducible poliovirus 2A protease expression in mammalian cells.
- To determine if poliovirus 2A protease can induce apoptosis in host cells.
Main Methods:
- Generation of a mammalian cell line with inducible expression of poliovirus 2A protease using the muristerone A-regulated system.
- Analysis of eukaryotic translation initiation factor 4GI (eIF4GI) and eIF4GII cleavage.
- Assessment of protein synthesis activity.
- Evaluation of cellular morphology, DNA fragmentation (TUNEL staining), and chromatin condensation to identify apoptosis.
Main Results:
- Inducible expression of poliovirus 2A protease led to cleavage of eIF4GI and eIF4GII.
- Cleavage of translation factors resulted in severe inhibition of cellular protein synthesis.
- Induced cells exhibited characteristic features of apoptosis, including nuclear fragmentation, chromatin condensation, and DNA laddering.
Conclusions:
- Expression of poliovirus 2A protease is sufficient to induce apoptosis in mammalian cells.
- The protease may induce apoptosis by inhibiting essential cellular mRNA translation or cleaving other cellular targets.
- Further research is needed to identify all cellular targets of poliovirus 2A protease involved in apoptosis induction.
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