Key result
The internal ribosome entry sites of poliovirus, CVB3, and HCV mediate translation in many organs, demonstrating that poliovirus tropism and attenuation are determined after internal ribosome entry.
Poliovirus tropism and attenuation are determined at a post-translational step, as IRES-mediated translation occurs in multiple organs regardless of their ability to support viral replication.
Suggests post-IRES determinants of poliovirus tropism; leaves open identification of tissue-specific replication factors in vivo.
Poliovirus replication is limited to a few organs, including the brain and spinal cord. This restricted tropism may be a consequence of organ-specific differences in translation initiation by the poliovirus internal ribosome entry site (IRES). A C-to-U mutation at base 472 in the IRES of the Sabin type 3 poliovirus vaccine strain, known to attenuate neurovirulence, may further restrict tropism by eliminating viral replication in the CNS. To determine the relationship between IRES-mediated translation and poliovirus tropism, recombinant human adenoviruses were used to express bicistronic mRNAs in murine organs. The IRESs of poliovirus, the cardiotropic coxsackievirus B3 (CVB3), and the hepatotropic hepatitis C virus (HCV) mediate translation in many organs, including those that do not support viral replication. A translation defect associated with the Sabin type 3 IRES was observed in all organs examined. Poliovirus type 1 and recombinant polioviruses dependent on the IRES of CVB3 or HCV replicate in the CNS of mice and cause paralysis. Although the type 3 Sabin strain is an effective vaccine, polioviruses with a U at base 472 of the IRES cause paralysis in newborn mice. Tropism of wild-type and vaccine strains of poliovirus is therefore determined after internal ribosome entry.
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Kauder et al. (2004) studied Poliovirus infection. Recombinant polioviruses and adenoviruses vs. Wild-type or alternative IRES constructs was evaluated on IRES-mediated translation and viral replication in murine organs. The internal ribosome entry sites of poliovirus, CVB3, and HCV mediate translation in many organs, demonstrating that poliovirus tropism and attenuation are determined after internal ribosome entry.
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