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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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