Two types of death of poliovirus-infected cells: Caspase involvement in the apoptosis but not cytopathic effect

The death of poliovirus-infected cells may occur in two forms: canonical cy topathic effect (CPE) (on productive infections) or apoptosis (when the vir al reproduction is hindered by certain drugs or some other restrictive cond itions). Morphological manifestations of the CPE and apoptosis, being disti nct, share some traits (e.g., chromatin condensation and nuclear deformatio n). it was shown here that a permeable caspase inhibitor, benzyloxycarbonyl -val-Ala-Asp-(OMe) fluoromethyl ketone (zVAD.fmk), prevented the developmen t of the poliovirus-induced apoptosis on abortive infection. The apoptotic pathway could be dissected by an inhibitor of chymotrypsin-like serine prot eases, N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), which prevented the cleavage of DNA to oligonucleosome-sized pieces and nuclear fragmentati on but did not suppress cellular shrinkage, cytoplasmic blebbing, and parti al chromatin condensation. These results demonstrate that caspase activatio n is involved in the execution phase of the viral apoptosis and suggest tha t a nuclear subset of me apoptotic program is under a separate control, inv olving a TPCK-sensitive event. Neither zVAD.fmk nor TPCK, at the concentrat ions affecting the apoptotic response, exerted appreciable influence on the virus growth or cellular pathological changes on productive infection, ind icating that the pathways leading to the poliovirus-evoked CPE and apoptosi s are different (C) 1998 Academic Press.