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Viruses 2015, 7(10), 5571-5586; doi:10.3390/v7102894

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
Received: 13 August 2015 / Revised: 17 October 2015 / Accepted: 18 October 2015 / Published: 26 October 2015
View Full-Text   |   Download PDF [1586 KB, uploaded 26 October 2015]   |  

Abstract

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
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

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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