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Open AccessArticle

Nucleobase but not Sugar Fidelity is Maintained in the Sabin I RNA-Dependent RNA Polymerase

1
Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA
2
Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Eric O. Freed
Viruses 2015, 7(10), 5571-5586; https://doi.org/10.3390/v7102894
Received: 13 August 2015 / Revised: 17 October 2015 / Accepted: 18 October 2015 / Published: 26 October 2015
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. View Full-Text
Keywords: enterovirus; poliovirus; Sabin; oral poliovirus vaccine; vaccine-associated paralytic poliovirus; vaccine-derived poliovirus; RNA-dependent RNA polymerase; polymerase fidelity enterovirus; poliovirus; Sabin; oral poliovirus vaccine; vaccine-associated paralytic poliovirus; vaccine-derived poliovirus; RNA-dependent RNA polymerase; polymerase fidelity
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Liu, X.; Musser, D.M.; Lee, C.A.; Yang, X.; Arnold, J.J.; Cameron, C.E.; Boehr, D.D. Nucleobase but not Sugar Fidelity is Maintained in the Sabin I RNA-Dependent RNA Polymerase. Viruses 2015, 7, 5571-5586.

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