Apoptosis-inducing and apoptosis-preventing functions of poliovirus

Abstract

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 cycloheximideinduced 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.

Cytopathic effects: virus-modulated manifestations of innate immunity?

“…Theiler's murine encephalomyelitis virus, a cardiovirus, elicits necrosis in permissive cells but triggers apoptosis in restrictive ones [46]. Although productive poliovirus infection of HeLa leads, as already said, to necrosis [8], infection of partially permissive promonocytic cells brings about apoptosis [47]. The difference in response to a virus is not necessarily related to the level of host permissiveness: poliovirus [48] and EMCV [49] may elicit apoptosis also in permissive cells.…”

“…The ability of picornaviruses to activate cellular apoptotic pathways was first discovered in poliovirus [8] and then described for numerous representatives of this viral family. The virus-triggered apoptosis appears to be an optional innate immunity reaction suppressing reproduction and spread of the pathogen.…”

“…To suppress the defensive apoptotic reaction, viruses have evolved antiapoptotic tools. Indeed, cells infected with poliovirus [8,14] and coxsackievirus [15] become resistant to nonviral apoptosis inducers. The dominance of antiapoptotic factors can be achieved by either downregulation of cellular proapoptotic activities or upregulation of antiapoptotic ones.…”

Enter the kill zone: Initiation of death signaling during virus entry

“…The combined requirement for receptor engagement and de novo synthesis of viral RNA and proteins for apoptosis induction by poliovirus observed in cells of the neuronal origin contradicts findings from studies of poliovirus-induced apoptosis of HeLa cells. Although productive poliovirus infection of HeLa cells does not evoke apoptosis, blockade of poliovirus infection prior to viral protein synthesis results in apoptosis (Tolskaya et al, 1995). Based on these findings, it has been proposed that the initial stages of poliovirus infection, which occur prior to translation of the incoming viral genome evoke prodeath signaling, whereas synthesis of viral proteins blocks apoptosis (Agol et al, 2000).…”

“…In order to overcome this host response, some viruses, especially those that replicate slowly and have genomes with larger coding capacity encode proteins that delay or prevent apoptotic cell death until viral replication is completed (Benedict et al, 2002;Hay and Kannourakis, 2002). Among viruses discussed in this review, a late event in poliovirus replication blocks apoptosis (Tolskaya et al, 1995) and ASFV encodes antiapoptotic proteins (Nogal et al, 2001;Galindo et al, 2008). In other cases, induction of apoptosis by a virus early in its replication cycle may be a viral immune evasion strategy.…”