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 cytopathic effect (CPE) (on productive infections) or apoptosis (when the viral reproduction is hindered by certain drugs or some other restrictive conditions). Morphological manifestations of the CPE and apoptosis, being distinct, share some traits (e.g., chromatin condensation and nuclear deformation). It was shown here that a permeable caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-(OMe) fluoromethyl ketone (zVAD.fmk), prevented the development of the poliovirus-induced apoptosis on abortive infection. The apoptotic pathway could be dissected by an inhibitor of chymotrypsin-like serine proteases, N-tosyl-l-phenylalanine chloromethyl ketone (TPCK), which prevented the cleavage of DNA to oligonucleosome-sized pieces and nuclear fragmentation but did not suppress cellular shrinkage, cytoplasmic blebbing, and partial chromatin condensation. These results demonstrate that caspase activation is involved in the execution phase of the viral apoptosis and suggest that a nuclear subset of the apoptotic program is under a separate control, involving a TPCK-sensitive event. Neither zVAD.fmk nor TPCK, at the concentrations affecting the apoptotic response, exerted appreciable influence on the virus growth or cellular pathological changes on productive infection, indicating that the pathways leading to the poliovirus-evoked CPE and apoptosis are different.
Agol
V I
VI
M. P. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow, Region 142782, Russia. viago@ipive.genebee.msu.su
Belov
G A
GA
Bienz
K
K
Egger
D
D
Kolesnikova
M S
MS
Raikhlin
N T
NT
Romanova
L I
LI
Smirnova
E A
EA
Tolskaya
E A
EA
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology*; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure / Q000821:virology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D019791:Guanidine / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D017955:Poliovirus / Q000472:pathogenicity / Q000502:physiology*; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D014108:Tosylphenylalanyl Chloromethyl Ketone; D020169:Caspases; D019791:Guanidine