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Journal of Virology, June 2000, p. 5534-5541, Vol. 74, No. 12
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Competing Death Programs in Poliovirus-Infected Cells: Commitment Switch in the Middle of the Infectious Cycle

Vadim I. Agol,1,2,* George A. Belov,1,2 Kurt Bienz,3 Denise Egger,3 Marina S. Kolesnikova,1 Lyudmila I. Romanova,1 Larissa V. Sladkova,4 and Elena A. Tolskaya1

M. P. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow Region 142782,1 M. V. Lomonosov Moscow State University, Moscow 119899,2 and Moscow Research Institute of Medical Ecology, Moscow 113149,4 Russia, and Institute for Medical Microbiology, University of Basel, CH-4003 Basel, Switzerland3

Received 16 November 1999/Accepted 18 March 2000

Productive poliovirus infection of HeLa cells leads to the canonical cytopathic effect (CPE), whereas certain types of abortive infection result in apoptosis. To define the time course of commitment to the different types of poliovirus-induced death, inhibitors of viral replication (guanidine HCl) or translation (cycloheximide) were added at different times postinfection (p.i.). Early in the infection (during the first ~2 h p.i.), predominantly proapoptotic viral function was expressed, rendering the cells committed to apoptosis, which developed several hours after viral expression was arrested. In the middle of infection, concomitantly with the onset of fast generation of viral progeny, the implementation of the viral apoptotic program was abruptly interrupted. In particular, activation of an Asp-Glu-Val-Asp (DEVD)-specific caspase(s) occurring in the apoptosis-committed cells was prevented by the ongoing productive infection. Simultaneously, the cells retaining normal or nearly normal morphology became committed to CPE, which eventually developed regardless of whether or not further viral expression was allowed to proceed. The implementation of the poliovirus-induced apoptotic program was suppressed in HeLa cells overexpressing the Bcl-2 protein, indicating that the fate of poliovirus-infected cells depends on the balance of host and viral pro- and antiapoptotic factors.


* Corresponding author. Mailing address: Institute of Poliomyelitis, Moscow Region 142782, Russia. Phone: 7 (095) 439 90 26. Fax: 7 (095) 439 93 21. E-mail: viago{at}ipive.genebee.msu.su.


Journal of Virology, June 2000, p. 5534-5541, Vol. 74, No. 12
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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