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RNA Virus Fidelity Mutants: A Useful Tool for Evolutionary Biology or a Complex Challenge?

RNA viruses replicate with low fidelity due to the error-prone nature of the RNA-dependent RNA polymerase, which generates approximately one mutation per round of genome replication. Due to the large population sizes produced by RNA viruses during replication, this results in a cloud of closely rela...

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Autores principales: Kautz, Tiffany F., Forrester, Naomi L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267201/
https://www.ncbi.nlm.nih.gov/pubmed/30388745
http://dx.doi.org/10.3390/v10110600
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author Kautz, Tiffany F.
Forrester, Naomi L.
author_facet Kautz, Tiffany F.
Forrester, Naomi L.
author_sort Kautz, Tiffany F.
collection PubMed
description RNA viruses replicate with low fidelity due to the error-prone nature of the RNA-dependent RNA polymerase, which generates approximately one mutation per round of genome replication. Due to the large population sizes produced by RNA viruses during replication, this results in a cloud of closely related virus variants during host infection, of which small increases or decreases in replication fidelity have been shown to result in virus attenuation in vivo, but not typically in vitro. Since the discovery of the first RNA virus fidelity mutants during the mid-aughts, the field has exploded with the identification of over 50 virus fidelity mutants distributed amongst 7 RNA virus families. This review summarizes the current RNA virus fidelity mutant literature, with a focus upon the definition of a fidelity mutant as well as methods to confirm any mutational changes associated with the fidelity mutant. Due to the complexity of such a definition, in addition to reports of unstable virus fidelity phenotypes, the future translational utility of these mutants and applications for basic science are examined.
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spelling pubmed-62672012018-12-07 RNA Virus Fidelity Mutants: A Useful Tool for Evolutionary Biology or a Complex Challenge? Kautz, Tiffany F. Forrester, Naomi L. Viruses Review RNA viruses replicate with low fidelity due to the error-prone nature of the RNA-dependent RNA polymerase, which generates approximately one mutation per round of genome replication. Due to the large population sizes produced by RNA viruses during replication, this results in a cloud of closely related virus variants during host infection, of which small increases or decreases in replication fidelity have been shown to result in virus attenuation in vivo, but not typically in vitro. Since the discovery of the first RNA virus fidelity mutants during the mid-aughts, the field has exploded with the identification of over 50 virus fidelity mutants distributed amongst 7 RNA virus families. This review summarizes the current RNA virus fidelity mutant literature, with a focus upon the definition of a fidelity mutant as well as methods to confirm any mutational changes associated with the fidelity mutant. Due to the complexity of such a definition, in addition to reports of unstable virus fidelity phenotypes, the future translational utility of these mutants and applications for basic science are examined. MDPI 2018-11-01 /pmc/articles/PMC6267201/ /pubmed/30388745 http://dx.doi.org/10.3390/v10110600 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kautz, Tiffany F.
Forrester, Naomi L.
RNA Virus Fidelity Mutants: A Useful Tool for Evolutionary Biology or a Complex Challenge?
title RNA Virus Fidelity Mutants: A Useful Tool for Evolutionary Biology or a Complex Challenge?
title_full RNA Virus Fidelity Mutants: A Useful Tool for Evolutionary Biology or a Complex Challenge?
title_fullStr RNA Virus Fidelity Mutants: A Useful Tool for Evolutionary Biology or a Complex Challenge?
title_full_unstemmed RNA Virus Fidelity Mutants: A Useful Tool for Evolutionary Biology or a Complex Challenge?
title_short RNA Virus Fidelity Mutants: A Useful Tool for Evolutionary Biology or a Complex Challenge?
title_sort rna virus fidelity mutants: a useful tool for evolutionary biology or a complex challenge?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267201/
https://www.ncbi.nlm.nih.gov/pubmed/30388745
http://dx.doi.org/10.3390/v10110600
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