23 Transgenic Mouse for the Study of Poliovirus Pathogenicity

Abstract

Poliomyelitis is an acute disease of the central nervous system (CNS) caused by poliovirus. Poliovirus is a human enterovirus that belongs to the Picornaviridae family and is classified into three stable serotypes, 1, 2, and 3 (Paul 1971). Humans are the only natural host of poliovirus, although poliovirus can be experimentally transferred to monkeys, in which it also causes a paralytic disease. Other animal species are not susceptible to most poliovirus strains. Because of this characteristic species specificity of poliovirus, monkeys and chimpanzees have been used as animal models for the studies of poliovirus pathogenicity.

In the 1950s, an outline of the pathology of poliomyelitis was established. According to this outline (Bodian 1955; Sabin 1956), poliovirus infection is initiated by ingestion of virus followed by its primary multiplication in the oropharynx and intestine (alimentary phase). Extensive viral multiplication is evident in tissues of the tonsils and Peyer’s patches of the ileum (lymphatic phase). From these sites, the virus moves into deep cervical and mesenteric lymph nodes, and then into the blood (viremic phase). Poliovirus invades the CNS through the blood-brain barrier or by the axonal pathway, and paralytic poliomyelitis occurs as a result of the destruction of neurons in the CNS, especially motor neurons in the anterior horn of the spinal cord and neurons of the motor cortex and the brain stem (neurological phase). Although many tissues are exposed to the virus during the viremic phase, sites of poliovirus replication are limited to certain tissues. Thus, poliovirus seems to have...