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

Xinran Liu, Derek M. Musser, Cheri A. Lee, Xiaorong Yang, Jamie J. Arnold, Craig E. Cameron, David D. Boehr

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Article numberA26
Pages (from-to)5571-5586
Number of pages16
JournalViruses
Volume7
Issue number10
DOIs
StatePublished - 2015

All Science Journal Classification (ASJC) codes

  • Infectious Diseases
  • Virology

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