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Poliovirus tropism and attenuation are determined after internal ribosome entry
Steven E. Kauder, Vincent R. Racaniello
Steven E. Kauder, Vincent R. Racaniello
Published June 15, 2004
Citation Information: J Clin Invest. 2004;113(12):1743-1753. https://doi.org/10.1172/JCI21323.
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Article Virology

Poliovirus tropism and attenuation are determined after internal ribosome entry

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Abstract

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.

Authors

Steven E. Kauder, Vincent R. Racaniello

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Figure 7

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Base at nucleotide 472 in poliovirus recovered from paralyzed mice. Uppe...
Base at nucleotide 472 in poliovirus recovered from paralyzed mice. Upper panel: Representative Southern blot hybridization of MboI-cleaved PCR products. The 93-bp DNA (472U) and 61-bp DNA (472C) are indicated. Lower panel: Proportion of 472U in each sample, determined by quantitative analysis of Southern blots. For mouse brain, data points are the mean of at least three mice except for P3/Sabin, for which one mouse was analyzed. Error bars indicate SD. The x axis indicates template for RT-PCR. Lane 1, plasmid DNA encoding P3/Sabin IRES; lane 2, plasmid DNA encoding P3/119/70 IRES; lanes 3_6, virus stocks used for infection of TgPVR mice; lanes 7_10, RNA from brain of TgPVR mice infected with the indicated virus stock.

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