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: Word count abstract: 10418 Word count manuscript without references, acknowledgement,figure legends: 240219 Number of Figures: 520 Author manuscript, published in "J Virol 82, 7 (2008) 3796-802"
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