Poliovirus induces apoptosis in the mouse central nervous system

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 motone urons is not well known. We investigated whether PV-induced central nervous system (CNS) injury is associated with apoptosis by using mice as animal m odels. Transgenic mice expressing the human PV receptor were infected intra cerebrally with either the neurovirulent PV-1 Mahoney strain or a paralytog enic dose of the attenuated PV-1 Sabin strain, Nontransgenic mice were infe cted with a mouse-adapted PV-1 Mahoney mutant. DNA fragmentation was demons trated in CNS tissue from paralyzed mice by visualization of DNA oligonucle osomal laddering and by enzyme-linked immunosorbent assay. Viral antigens a nd DNA fragmentation detected by the in situ terminal deoxynucleotidyltrans ferase-mediated dUTP-biotin nick end-labeling technique were colocalized in neurons of spinal cords from paralyzed mice. In addition, morphological ch anges characteristic of cells undergoing apoptosis were observed in motoneu rons by electron microscopy. Thus, we show that PV multiplication and CNS i njury during paralytic poliomyelitis are associated with apoptosis.