ArticleThe Journal of biological chemistry2013
Vaccine-derived mutation in motif D of poliovirus RNA-dependent RNA polymerase lowers nucleotide incorporation fidelity.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Identification of fidelity-determined residues of Porcine reproductive and respiratory syndrome virus through structural alignment.Virulence · 2026Article
- Targeting the Rift Valley Fever Virus Polymerase: Resistance Mechanisms and Structural Insights.ACS infectious diseases · 2025Article
- Fidelity Characterization of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and NADC30-like Strain.Viruses · 2024Article
- Picornavirus 3C Proteins Intervene in Host Cell Processes through Proteolysis and Interactions with RNA.Viruses · 2023Review
- Designing an Epitope-Based Peptide Vaccine Derived from RNA-Dependent RNA Polymerase (RdRp) against Dengue Virus Serotype 2.Vaccines · 2022Article
- The Second Human Pegivirus, a Non-Pathogenic RNA Virus with Low Prevalence and Minimal Genetic Diversity.Viruses · 2022Review
- Review
- Article
- Animal and human RNA viruses: genetic variability and ability to overcome vaccines.Archives of microbiology · 2021Review
- Polymerase Fidelity Contributes to Foot-and-Mouth Disease Virus Pathogenicity and TransmissibilityJournal of virology · 2020Article
- A Low Fidelity Virus Shows Increased Recombination during the Removal of an Alphavirus Reporter Gene.Viruses · 2020Article
- 2'-C-methylated nucleotides terminate virus RNA synthesis by preventing active site closure of the viral RNA-dependent RNA polymerase.The Journal of biological chemistry · 2019Article
- Rational Control of Poliovirus RNA-Dependent RNA Polymerase Fidelity by Modulating Motif-D Loop Conformational Dynamics.Biochemistry · 2019Article
- Naturally occurring mutations in PB1 affect influenza A virus replication fidelity, virulence, and adaptability.Journal of biomedical science · 2019Article
- RNA Virus Fidelity Mutants: A Useful Tool for Evolutionary Biology or a Complex Challenge?Viruses · 2018Review
- Contribution of a Multifunctional Polymerase Region of Foot-and-Mouth Disease Virus to Lethal Mutagenesis.Journal of virology · 2018Article
- Foot-and-mouth disease virus type O specific mutations determine RNA-dependent RNA polymerase fidelity and virus attenuation.Virology · 2018Article
- Structural and Functional Basis of the Fidelity of Nucleotide Selection by Flavivirus RNA-Dependent RNA Polymerases.Viruses · 2018Review
- Article
- Attenuation of Foot-and-Mouth Disease Virus by Engineered Viral Polymerase Fidelity.Journal of virology · 2017Article
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9 authors.
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Abstract
All viral RNA-dependent RNA polymerases (RdRps) have a conserved structural element termed motif D. Studies of the RdRp from poliovirus (PV) have shown that a conformational change of motif D leads to efficient and faithful nucleotide addition by bringing Lys-359 into the active site where it serves as a general acid. The RdRp of the Sabin I vaccine strain has Thr-362 changed to Ile. Such a drastic change so close to Lys-359 might alter RdRp function and contribute in some way to the attenuated phenotype of Sabin type I. Here we present our characterization of the T362I RdRp. We find that the T362I RdRp exhibits a mutator phenotype in biochemical experiments in vitro. Using NMR, we show that this change in nucleotide incorporation fidelity correlates with a change in the structural dynamics of motif D. A recombinant PV expressing the T362I RdRp exhibits normal growth properties in cell culture but expresses a mutator phenotype in cells. For example, the T362I-containing PV is more sensitive to the mutagenic activity of ribavirin than wild-type PV. Interestingly, the T362I change was sufficient to cause a statistically significant reduction in viral virulence. Collectively, these studies suggest that residues of motif D can be targeted when changes in nucleotide incorporation fidelity are desired. Given the observation that fidelity mutants can serve as vaccine candidates, it may be possible to use engineering of motif D for this purpose.
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