Key result
The nucleotide incorporation rate and nucleobase fidelity of the Sabin I RNA-dependent RNA polymerase were similar to the wild-type enzyme, suggesting nucleobase fidelity does not contribute to viral attenuation.
The nucleobase fidelity of the Sabin I RdRp is maintained near wild-type levels, suggesting it likely does not contribute to viral attenuation.
Does not implicate nucleobase fidelity in Sabin attenuation; leaves open alternative mechanisms for poliovirus research.
The Sabin I poliovirus live, attenuated vaccine strain encodes for four amino acid changes (i.e., D53N, Y73H, K250E, and T362I) in the RNA-dependent RNA polymerase (RdRp). We have previously shown that the T362I substitution leads to a lower fidelity RdRp, and viruses encoding this variant are attenuated in a mouse model of poliovirus. Given these results, it was surprising that the nucleotide incorporation rate and nucleobase fidelity of the Sabin I RdRp is similar to that of wild-type enzyme, although the Sabin I RdRp is less selective against nucleotides with modified sugar groups. We suggest that the other Sabin amino acid changes (i.e., D53N, Y73H, K250E) help to re-establish nucleotide incorporation rates and nucleotide discrimination near wild-type levels, which may be a requirement for the propagation of the virus and its efficacy as a vaccine strain. These results also suggest that the nucleobase fidelity of the Sabin I RdRp likely does not contribute to viral attenuation.
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Liu et al. (2015) studied Poliovirus. Sabin I RNA-dependent RNA polymerase vs. Wild-type enzyme was evaluated on Nucleotide incorporation rate and nucleobase fidelity. The nucleotide incorporation rate and nucleobase fidelity of the Sabin I RNA-dependent RNA polymerase were similar to the wild-type enzyme, suggesting nucleobase fidelity does not contribute to viral attenuation.
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