Poliovirus neuropathogenicity depends on sequences within the 5' nontransla
ted region of the virus. Exchange of the poliovirus internal ribosomal entr
y site with its counterpart from human rhinovirus type 2 resulted in attenu
ation of neurovirulence in primates. Despite deficient virus propagation in
cells of neuronal origin, nonpathogenic polio recombinants retain excellen
t growth characteristics in cell lines derived from glial neoplasms. Suscep
tibility of malignant glioma cells to poliovirus may be mediated by express
ion of a poliovirus receptor, CD155. in glial neoplasms. Intergeneric polio
recombinants with heterologous internal ribosomal entry site elements unfo
lded strong oncolytic potential against experimentally induced gliomas in a
thymic mice. Our observations suggest that highly attenuated poliovirus rec
ombinants may have applicability as biotherapeutic antineoplastic agents.