Canine distemper virus infection of primary hippocampal cells induces increase in extracellular glutamate and neurodegeneration.
The canine distemper virus (CDV) belongs to the Morbillivirus genus which includes important human pathogens like the closely related measles virus. CDV infection can reach the nervous system where it causes serious malfunctions. Although this pathology is well described, the molecular events in brain infection are still poorly understood. Here we studied infection in vitro by CDV using a model of dissociated cell cultures from newborn rat hippocampus. We used a recombinant CDV closely related to the neurovirulent A75/17 which also expresses the enhanced green fluorescent protein. We found that infected neurons and astrocytes could be clearly detected, and that infection spreads only slowly to neighboring cells. Interestingly, this infection causes a massive cell death of neurons, which includes also non-infected neurons. Antagonists of NMDA-type or alpha-amino-3-hydroxy-5-methylisoxazole-4-propinate (AMPA)-type glutamate receptors could slow down this neuron loss, indicating an involvement of the glutamatergic system in the induction of cell death in infected and non-infected cells. Finally, we show that, following CDV infection, there is a steady increase in extracellular glutamate in infected cultures. These results indicate that CDV infection induces excitotoxic insults on neurons via glutamatergic signaling.
Institut de Biotechnologie, University of Lausanne, Lausanne, Switzerland.
Jean-Marc
JM
Brunner
Philippe
P
Plattet
Paul
P
Majcherczyk
Andreas
A
Zurbriggen
Riccardo
R
Wittek
Harald
H
Hirling
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism / Q000821:virology; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004216:Distemper / Q000378:metabolism* / Q000503:physiopathology; D004217:Distemper Virus, Canine / Q000472:pathogenicity / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D045604:Extracellular Fluid / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism / Q000503:physiopathology / Q000821:virology; D018698:Glutamic Acid / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology*; D009410:Nerve Degeneration / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology*; D009474:Neurons / Q000378:metabolism / Q000821:virology; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins; D015854:Up-Regulation / Q000502:physiology; D014709:Vero Cells
D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid