The major apoptotic pathway activated and suppressed by poliovirus

Area of Science:

• Cell Biology
• Virology
• Molecular Biology

Background:

• Poliovirus infection typically induces apoptosis, a programmed cell death pathway.
• Viral antiapoptotic functions often counteract this cellular response.
• Mitochondrial pathways play a crucial role in initiating apoptosis.

Purpose of the Study:

• To investigate the role of mitochondrial apoptosis in poliovirus-infected cells.
• To elucidate the mechanisms by which poliovirus suppresses apoptosis.
• To identify key viral and cellular factors involved in apoptosis regulation during infection.

Main Methods:

• Cell culture (HeLa, MCF-7 derivatives) infected with poliovirus.
• Analysis of cytochrome c release from mitochondria.
• Western blotting to detect procaspase-9 and active caspase-9 levels.
• Assessment of Bid protein truncation.
• Overexpression of Bcl-2 to study its effect on apoptosis.
• Evaluation of apoptosis hallmarks like chromatin condensation and DNA degradation.

Main Results:

• Poliovirus infection caused cytochrome c efflux from mitochondria in both abortive and productive infections.
• Bid truncation occurred in abortive but not productive infections.
• Overexpression of Bcl-2 suppressed virus-induced cytochrome c efflux.
• Procaspase-9 levels decreased, with active caspase-9 accumulating in abortive infections.
• Productive infections showed aberrant procaspase-9 processing and degradation, preventing active caspase-9 formation.
• Caspase-9 and caspase-3 were essential for apoptosis execution.

Conclusions:

• Poliovirus infection initiates apoptosis via mitochondrial pathways, involving cytochrome c release and caspase activation.
• Viral antiapoptotic mechanisms suppress apoptosis downstream of cytochrome c release, partly through aberrant procaspase-9 processing.
• Bid processing and viral strategies targeting caspases contribute to the suppression of apoptosis during productive poliovirus infection.