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Imprecise recombinant viruses evolve via a fitness-driven, iterative process of polymerase template-switching events

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Bentley_2021_PLoS_Pathogens_Imprecis_recombinant_viruses_CC.pdf (2.463Mb)
Date
20/08/2021
Author
Bentley, Kirsten
Alnaji, Fadi Ghassan
Woodford, Luke
Jones, Siân
Woodman, Andrew
Evans, David J.
Funder
The Wellcome Trust
The Wellcome Trust
BBSRC
Grant ID
BB/M009343/1
Keywords
QH301 Biology
QR355 Virology
DAS
SDG 3 - Good Health and Well-being
Metadata
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Abstract
Viruses with positive-sense RNA genomes, such as poliovirus, have several mechanisms by which they evolve. One of these is the process of recombination involving the large-scale exchange of genetic information. Recombination occurs during replication when the viral polymerase, bound to the nascent RNA chain, switches from copying one genome to another. However, the polymerase does not always accurately switch between the two, resulting in sequence duplications or deletions, and genomes that are referred to as imprecise. Over multiple rounds of replication sequence duplications are lost and genomes are resolved to wild type length, but it is unclear how this occurs. Here we used synthetic polioviruses containing defined sequence duplications to determine that the genome population undergoes repeated rounds of recombination until sequence duplications are lost and viruses with precise, wild type length genomes are selected for. This selection is based on the overall fitness of the virus population, with less fit imprecise viruses evolving more quickly. Our study suggests that recombination is a continual process where virus fitness drives the selection of a small subset of recombinant variants. These data are important for understanding how novel viruses evolve via recombination and how this process can be blocked to prevent novel and dangerous pathogens from arising.
Citation
Bentley , K , Alnaji , F G , Woodford , L , Jones , S , Woodman , A & Evans , D J 2021 , ' Imprecise recombinant viruses evolve via a fitness-driven, iterative process of polymerase template-switching events ' , PLoS Pathogens , vol. 17 , no. 8 , e1009676 . https://doi.org/10.1371/journal.ppat.1009676
Publication
PLoS Pathogens
Status
Peer reviewed
DOI
https://doi.org/10.1371/journal.ppat.1009676
ISSN
1553-7366
Type
Journal article
Rights
Copyright: © 2021 Bentley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description
Funding: This work was supported by the Biotechnology and Biological Sciences Research Council - https://bbsrc.ukri.org/ - (BB/M009343/1 to D.J.E) and an ISSF award from The Wellcome Trust - https://wellcome.org/ - to the BSRC, University of St Andrews. F.G.A was supported by a PhD studentship from the Ministry of Education, Government of Saudi Arabia. S.J was supported by a Microbiology Society - https://microbiologysociety.org/ - Harry Smith Vacation Studentship awarded to K.B.
Collections
  • University of St Andrews Research
URI
http://hdl.handle.net/10023/23906

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