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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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