An ex vivo murine model to study poliovirus-induced apoptosis in nerve cells.
Paralytic poliomyelitis results from destruction of motor neurons owing to poliovirus (PV) replication. Using a mouse model, we have previously shown that PV kills neurons of the central nervous system (CNS) as a result of apoptosis (Girard et al., Journal of Virology 73, 6066-6072, 1999). We report the development of mixed mouse primary nerve cell cultures from the cerebral cortex of neonatal mice transgenic for the human PV receptor. These cultures contained all three main cell types of the CNS, i.e. neurons, astrocytes and oligodendrocytes. All three cell types were susceptible to PV infection and virus replication in the cultures led to DNA fragmentation characteristic of apoptosis. PV-induced apoptosis was inhibited by the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(O-Me) fluoromethyl ketone (Z-VAD.FMK), indicating that this process involved caspases. Thus, these mixed mouse primary nerve cell cultures are a new in vitro model for studying the molecular mechanisms of PV-induced apoptosis in nerve cells.
Unité de Neurovirologie et Régénération du Système Nerveux, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris cedex 15, France1.
Thérèse
T
Couderc
Unité de Neurovirologie et Régénération du Système Nerveux, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris cedex 15, France1.
Florence
F
Guivel-Benhassine
Unité de Neurovirologie et Régénération du Système Nerveux, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris cedex 15, France1.
Viviane
V
Calaora
Unité de Neurovirologie et Régénération du Système Nerveux, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris cedex 15, France1.
Anne-Sophie
AS
Gosselin
Unité de Neurovirologie et Régénération du Système Nerveux, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris cedex 15, France1.
Bruno
B
Blondel
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000502:physiology / Q000821:virology*; D017955:Poliovirus / Q000472:pathogenicity* / Q000502:physiology; D011991:Receptors, Virus / Q000235:genetics
D008565:Membrane Proteins; D011991:Receptors, Virus; C066100:poliovirus receptor