Nucleobase but not sugar fidelity is maintained in the Sabin I RNA-dependent RNA polymerase

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Liu, X.
- Other Affiliation: The Pennsylvania State University
Musser, D.M.
- Other Affiliation: The Pennsylvania State University
Lee, C.A.
- Other Affiliation: The Pennsylvania State University
Yang, X.
- Other Affiliation: The Pennsylvania State University
Arnold, J.J.
- Other Affiliation: The Pennsylvania State University
Cameron, C.E.
- School of Medicine, Department of Microbiology and Immunology
- Other Affiliation: The Pennsylvania State University
Boehr, D.D.
- Other Affiliation: The Pennsylvania State University

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.

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