Variability in apoptotic response to poliovirus infection

Lomonosov Moscow State University, Moskva, Moscow, Russia
Virology (Impact Factor: 3.32). 02/2005; 331(2):292-306. DOI: 10.1016/j.virol.2004.10.038
Source: PubMed


In several cell types, poliovirus activates the apoptotic program, implementation of which is suppressed by viral antiapoptotic functions. In such cells, productive infection leads to a necrotic cytopathic effect (CPE), while abortive reproduction, associated with inadequate viral antiapoptotic functions, results in apoptosis. Here, we describe two other types of cell response to poliovirus infection. Murine L20B cells expressing human poliovirus receptor responded to the infection by both CPE and apoptosis concurrently. Interruption of productive infection decreased rather than increased the proportion of apoptotic cells. Productive infection was accompanied by the early efflux of cytochrome c from the mitochondria in a proportion of cells and by activation of DEVD-specific caspases. Inactivation of caspase-9 resulted in a marked, but incomplete, prevention of the apoptotic response of these cells to viral infection. Thus, the poliovirus-triggered apoptotic program in L20B cells was not completely suppressed by the viral antiapoptotic functions. In contrast, human rhabdomyosarcoma RD cells did not develop appreciable apoptosis during productive or abortive infection, exhibiting inefficient efflux of cytochrome c from mitochondria and no marked activation of DEVD-specific caspases. The cells were also refractory to several nonviral apoptosis inducers. Nevertheless, typical caspase-dependent signs of apoptosis in a proportion of RD cells were observed after cessation of viral reproduction. Such "late" apoptosis was also observed in productively infected HeLa cells. In addition, a tiny proportion of all studied cells were TUNEL positive even in the presence of a caspase inhibitor. Degradation of DNA in such cells appeared to be a postmortem phenomenon. Biological relevance of variable host responses to viral infection is discussed.

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Available from: George A Belov, Sep 04, 2014
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    • "The cell line used could also influence the development of apoptosis. Moreover, the reaction of the host apoptotic machinery to picornavirus infection has been reported to be generally cell-dependent and affected by the cell's environment, the status of its differentiation, and the genotype (Romanova et al., 2005). In agreement with our results, the apoptotic programme induced by PV in murine cells involves damaged mitochondria, efflux of cytochrome c, and activation of caspase-9, followed by activation of downstream effector caspases. "
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    ABSTRACT: The virus-encoded viroporins are known to modify membrane permeability and play an essential role in virus budding. Here, a comparative analysis of the membrane permeabilization capacity of a number of viroporins was performed in baby hamster kidney cells. Synthesis of 6K protein from Sindbis virus, E from mouse hepatitis virus, M2 from influenza A virus, and 2B and 3A from poliovirus enhanced membrane permeability to different extents. We show that two proteins from hepatitis C virus, p7 and NS4A, also display viroporin activity to a level comparable to 6K protein. In addition to their capacity to disrupt ionic cellular homeostasis and promote bacterial cell lysis, the expressed viroporins were able to induce cell death. Degradation of internucleosomal DNA and generation of apoptotic bodies were observed upon viroporin expression. Consistently, cleavage of translation initiation factor 4GI and poly-(ADP-ribose) polymerase indicated activation of effector caspase-3. We found that poliovirus 2B localizes partially in mitochondria and induces an anomalous perinuclear distribution of these organelles. Mitochondria morphology was also altered after expression of other viroporins. Finally, detection of cytochrome c release from mitochondria suggests involvement of the mitochondrial pathway in viroporin-induced apoptosis. These findings suggest that viroporins induce caspase-dependent programmed cell death.
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    • "Notably, RD cells are derived from muscle tissue, and may offer some insights into the neuromuscular diseases caused by EV71, thus further warranting their use. Signs of late apoptotic responses detectable after the phase of active virus growth and the development of CPE (Romanova et al., 2005) in RD cells allowed us to probe into the apoptosis-evading mechanism during productive infection. Pelletier et al. (1998) stated Fig. 5. Identification of six differentially expressed proteins by two-dimensional proteomic analysis of uninfected (U) and EV71 MS/7423/87 straininfected (I) RD cell samples at 8 and 20 h p.i. "
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