Molecular pathogenesis of type 2 poliovirus in mice

Lansing strain of poliovirus type 2 (PV-2) produces a fatal paralytic disease in mice after intracerebral inoculation. To identify virus-containing nerve cells in poliovirus-infected mice, we developed a technique of in situ hybridization for viral RNA with a poliovirus-specific riboprobe. Large numbers of genomes were found in motoneurons and their processes, as well as in ghosts of neurons with or without inflammatory cells. This indicates that the death of motoneurons is due to a direct effect of viral replication. The presence of viral RNA in neuronal processes suggests an axonal dissemination of poliovirus within the central nervous system (CNS). Detection of viral genomes in small cells located in anterior and in posterior horns shows that motoneurons are not the only cells susceptible to poliovirus in the CNS. To see if PV-2/Lansing still exits in nature, PV-2 isolated from the CNS and from the gut of two human cases of paralytic poliomyelitis were characterized by determining epitope maps and phenotypic markers and by sequencing regions of the genome coding for antigenic sites and the 5' non-coding region. Comparison of virus isolated from the intestine and from the CNS of the same subject revealed a high degree of homology, suggesting that virus isolated from the gut is representative of virus in the neuronal lesions. The isolate from a case had more homology to PV-2/Lansing, whereas the other isolate showed more homology to PV-2/Sabin. These results show that, despite intensive vaccination with oral polio vaccine for 25 years, wild PV-2/Lansing-like viruses, pathogenic for mice, still circulate in nature ad induce human paralytic cases.