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Poliovirus induces apoptosis in the mouse central nervous system
S Girard1, T Couderc, J Destombes
1Unité de Neurovirologie et Régénération du Système Nerveux, Institut Pasteur, 75724 Paris cedex 15, France.
Abstract:
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.
Insights
Poliovirus infection causes paralysis by destroying motoneurons. This study reveals that poliovirus-induced central nervous system injury involves apoptosis, a programmed cell death process.
Area of Science:
- Neuroscience
- Virology
- Cell Biology
Background:
- Poliovirus (PV) causes paralytic poliomyelitis through motoneuron destruction.
- The precise mechanism of PV-induced motoneuron death remains unclear.
- Apoptosis, or programmed cell death, is a potential pathway for neuronal injury.
Purpose of the Study:
- To investigate the association between poliovirus-induced central nervous system (CNS) injury and apoptosis.
- To elucidate the cellular mechanisms underlying motoneuron death in paralytic poliomyelitis.
Main Methods:
- Mice models were used, including transgenic mice expressing the human PV receptor.
- Mice were intracerebrally infected with different poliovirus strains (PV-1 Mahoney, PV-1 Sabin).
- Apoptosis was assessed using DNA fragmentation assays (laddering, ELISA), in situ labeling, and electron microscopy.
Main Results:
- DNA fragmentation, a hallmark of apoptosis, was detected in the CNS of paralyzed mice.
- Viral antigens and DNA fragmentation were colocalized within spinal cord neurons.
- Electron microscopy revealed morphological evidence of apoptosis in motoneurons.
Conclusions:
- Poliovirus multiplication and CNS injury in paralytic poliomyelitis are linked to apoptotic cell death.
- Apoptosis plays a significant role in the pathogenesis of poliovirus-induced paralysis.
- Understanding this process may inform therapeutic strategies against poliovirus infection.