Cells respond to poliovirus
infection by switching on the apoptotic program, implementation of which is usually suppressed by viral antiapoptotic functions. We show here that poliovirus
infection of HeLa cells or derivatives of MCF-7 cells was accompanied by the efflux of
cytochrome c from mitochondria. This efflux occurred during both abortive
infection (e.g., interrupted by
guanidine-HCl and ending with apoptosis) and productive
infection (leading to cytopathic effect). The former type of
infection, but not the latter, was accompanied by truncation of the proapoptotic
protein Bid. The virus-triggered
cytochrome c efflux was suppressed by overexpression of Bcl-2. Both abortive and productive
infections also resulted in a decreased level of
procaspase-9, as revealed by Western blotting. In the former case, this decrease was accompanied by the accumulation of a
protein with the electrophoretic mobility of active
caspase-9. In contrast, in the productively infected cells, the latter
protein was absent but caspase-9-related
polypeptides with altered mobility could be detected. Both
caspase-9 and
caspase-3 were shown to be essential for the development of such hallmarks of virus-induced apoptosis as
chromatin condensation,
DNA degradation, and nuclear fragmentation. These and some other results suggest the following scenario. Poliovirus
infection activates the apoptotic pathway, involving mitochondrial damage,
cytochrome c efflux, and consecutive activation of
caspase-9 and
caspase-3. The apoptotic signal appears to be amplified by a loop which includes secondary processing of Bid. The implementation of the apoptotic program in productively infected cells may be suppressed, however, by the viral antiapoptotic functions, which act at a step(s) downstream of the
cytochrome c efflux. The suppression appears to be caused, at least in part, by aberrant processing and degradation of
procaspase-9.