Apoptosis-inducing and apoptosis-preventing functions of poliovirus.
Data showing that an apoptotic reaction (the exit into the cytoplasm and nucleolytic internucleosomal degradation of chromosomal DNA, compaction and fragmentation of chromatin, cellular shrinkage, and cytoplasmic blebbing) developed in a subline of HeLa-S3 cells upon nonpermissive poliovirus infection with either a guanidine-sensitive poliovirus in the presence of guanidine, a guanidine-dependent mutant in the absence of guanidine, or certain temperature-sensitive mutants at a restrictive temperature are presented. Essentially, no apoptotic reaction occurred upon permissive infection of these cells. Both permissive and nonpermissive infections resulted in the inhibition of host protein synthesis. Actinomycin D or cycloheximide also elicited a rapid apoptotic reaction in uninfected cells. However, preinfection or coinfection with poliovirus prevented the apoptotic response to the addition of actinomycin D, and preinfection blocked cycloheximide-induced apoptosis as well. These data fit a model in which the cells used are prepared to develop apoptosis, with their viability due to the presence of certain short-lived mRNA and protein species. Poliovirus infection turns on two oppositely directed sets of reactions. On the one hand, the balance is driven toward apoptosis, probably via the shutoff of host macromolecular synthesis. On the other hand, viral protein exhibits antiapoptotic activity, thereby preventing premature cell death. To our knowledge, this is the first description of an antiapoptotic function for an RNA virus.
Tolskaya
E A
EA
Institute of Poliomyelitis & Viral Encephalitides, Russian Academy of Medical Sciences, Moscow Region.
Romanova
L I
LI
Kolesnikova
M S
MS
Ivannikova
T A
TA
Smirnova
E A
EA
Raikhlin
N T
NT
Agol
V I
VI
D017209:Apoptosis; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D017955:Poliovirus / Q000502:physiology*; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis
D003609:Dactinomycin; D012313:RNA; D003513:Cycloheximide