Picornaviruses Poliovirus

Poliovirus (PV) is a nonenveloped, positive-stranded RNA virus, which is responsible for causing poliomyelitis. PV RNA is composed of a 5'-nontranslated region that contains an internal ribosomal entry site (IRES) which directs the synthesis of a single polypeptide that is subsequently processed by viral proteases into structural and nonstructural proteins (75). Polioviruses tropism is restricted to cells expressing CD155, a member of the Ig superfamily, which is prevalent on lower motor neurons resident within the spinal cord and brainstem (138). The IRES elements encode strong cell-type specific restrictions and probably play a key role in the neurovirulent behavior of the virus. It subsequently became apparent, that other viruses, such as hepatitis C virus (HCV) or rhinoviruses also contain IRES elements. Experiments into the importance of the IRES elements lead to creation of a poliovirus chimera (referred to as PV1) (139), which contained the human rhinovirus type 2 IRES element. PV1 was noted to be avirulent and generally nonpathogenic, even in primates. However PV1 was noted to grow well in tissue cultured cells derived from malignant gliomas, for reasons that remain unknown, but could speculatively involve defects in the innate immune responses or an upregulation of translation rates (139). PV1 showed oncolytic potential in experimentally induced gliomas in athymic nude mice and may thus be useful for the treatment of cancers expressing CD155, which, may include other tumors in addition to those of brain cancer origin (140). Subsequent studies have also demonstrated that live attenuated poliovirus exhibits oncolytic activity against neuroblastoma, in vitro and in vivo and other picornoviruses such as bovine enterovirus (BEV) may share similar traits (141).

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