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Journal of Virology, July 1999, p. 6066-6072, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Poliovirus Induces Apoptosis in the Mouse Central
Nervous System
Sophie
Girard,1
Thérèse
Couderc,1,*
Josette
Destombes,2
Danièle
Thiesson,2
Francis
Delpeyroux,3 and
Bruno
Blondel1,*
Unité de Neurovirologie et
Régénération du Système
Nerveux1 and Laboratoire
d'Epidémiologie Moléculaire des
Entérovirus,3 Institut Pasteur, 75724 Paris cedex 15, and URA CNRS 2115, Laboratoire du Cytosquelette
et Développement, Faculté de Médecine
Pitié-Salpétrière, 75634 Paris cedex
13,2 France
Received 28 December 1998/Accepted 23 March 1999
Poliovirus (PV) is the etiological agent of human paralytic
poliomyelitis. Paralysis results from the destruction of motoneurons, a
consequence of PV replication. However, the PV-induced process leading
to the death of motoneurons is not well known. We investigated whether
PV-induced central nervous system (CNS) injury is associated with
apoptosis by using mice as animal models. Transgenic mice expressing
the human PV receptor were infected intracerebrally with either the
neurovirulent PV-1 Mahoney strain or a paralytogenic dose of the
attenuated PV-1 Sabin strain. Nontransgenic mice were infected with a
mouse-adapted PV-1 Mahoney mutant. DNA fragmentation was demonstrated
in CNS tissue from paralyzed mice by visualization of DNA
oligonucleosomal laddering and by enzyme-linked immunosorbent assay.
Viral antigens and DNA fragmentation detected by the in situ terminal
deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling
technique were colocalized in neurons of spinal cords from paralyzed
mice. In addition, morphological changes characteristic of cells
undergoing apoptosis were observed in motoneurons by electron
microscopy. Thus, we show that PV multiplication and CNS injury during
paralytic poliomyelitis are associated with apoptosis.
*
Corresponding author. Mailing address: Unité de
Neurovirologie et Régénération du
Système Nerveux, Institut Pasteur, 28 rue du Docteur Roux,
75724 Paris cedex 15, France. Phone: (33) 1.45.68.87.62. Fax: (33)
1.40.61.34.21. E-mail: bblondel{at}pasteur.fr and
tcouderc{at}pasteur.fr.
Journal of Virology, July 1999, p. 6066-6072, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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