APOPTOSIS-INDUCING AND APOPTOSIS-PREVENTING FUNCTIONS OF POLIOVIRUS

Data showing that an apoptotic reaction (the exit into the cytoplasm a nd nucleolytic internucleosomal degradation of chromosomal DNA, compac tion and fragmentation of chromatin, cellular shrinkage, and cytoplasm ic blebbing) developed in a subline of HeLa-S3 cells upon nonpermissiv e poliovirus infection with either a guanidine-sensitive poliovirus in the presence of guanidine, a guanidine-dependent mutant in the absenc e of guanidine, or certain temperature-sensitive mutants at a restrict ive temperature are presented. Essentially, no apoptotic reaction occu rred upon permissive infection of these cells. Both permissive and non permissive infections resulted in the inhibition of host protein synth esis. Actinomycin D or cycloheximide also elicited a rapid apoptotic r eaction in uninfected cells. However, preinfection or coinfection with poliovirus prevented the apoptotic response to the addition of actino mycin D, and preinfection blocked cycloheximide-induced apoptosis as w ell. These data fit a model in which the cells used are prepared to de velop apoptosis, with their viability due to the presence of certain s hort-lived mRNA and protein species. Poliovirus infection turns on two oppositely directed sets of reactions. On the one hand, the balance i s driven toward apoptosis, probably via the shutoff of host macromolec ular synthesis. On the other hand, viral protein exhibits antiapoptoti c activity, thereby preventing premature cell death. To our knowledge, this is the first description of an antiapoptotic Function for an RNA virus.