Competing death programs in poliovirus-infected cells: commitment switch in the middle of the infectious cycle

Productive poliovirus infection of HeLa cells leads to the canonical cytopa thic effect (CPE), whereas certain types of abortive infection result in ap optosis, To define the time course of commitment to the different types of poliovirus induced death, inhibitors of viral replication (guanidine HCl) o r translation (cycloheximide) were added at different times postinfection ( p.i.), Early in the infection (during the first similar to 2 h p.i.), predo minantly proapoptotic viral function was expressed, rendering the cells com mitted to apoptosis, which developed several hours after viral expression w as arrested. In the middle of infection, concomitantly with the onset of fa st generation of viral progeny, the implementation of the viral apoptotic p rogram was abruptly interrupted. In particular, activation of an Asp-Glu-Va l-Asp (DEVD)-specific caspase(s) occurring in the apoptosis-committed cells was prevented by the ongoing productive infection. Simultaneously, the cel ls retaining normal or nearly normal morphology became committed to CPE, wh ich eventually developed regardless of whether or not further viral express ion was allowed to proceed, The implementation of the poliovirus-induced ap optotic program was suppressed in HeLa cells overexpressing the Bcl-2 prote in, indicating that the fate of poliovirus infected cells depends on the ba lance of host and viral pro- and antiapoptotic factors.