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Recombination in enteroviruses is a biphasic replicative process involving the generation of greater-than genome length 'imprecise' intermediates
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Lowry, Kym, Woodman, Andrew, Cook, Jonathan P. and Evans, David J. (2014) Recombination in enteroviruses is a biphasic replicative process involving the generation of greater-than genome length 'imprecise' intermediates. PLoS Pathogens, Volume 10 (Number 6). Article number e1004191. doi:10.1371/journal.ppat.1004191 ISSN 1553-7374.
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Official URL: http://dx.doi.org/10.1371/journal.ppat.1004191
Abstract
Recombination in enteroviruses provides an evolutionary mechanism for acquiring extensive regions of novel sequence, is suggested to have a role in genotype diversity and is known to have been key to the emergence of novel neuropathogenic variants of poliovirus. Despite the importance of this evolutionary mechanism, the recombination process remains relatively poorly understood. We investigated heterologous recombination using a novel reverse genetic approach that resulted in the isolation of intermediate chimeric intertypic polioviruses bearing genomes with extensive duplicated sequences at the recombination junction. Serial passage of viruses exhibiting such imprecise junctions yielded progeny with increased fitness which had lost the duplicated sequences. Mutations or inhibitors that changed polymerase fidelity or the coalescence of replication complexes markedly altered the yield of recombinants (but did not influence non-replicative recombination) indicating both that the process is replicative and that it may be possible to enhance or reduce recombination-mediated viral evolution if required. We propose that extant recombinants result from a biphasic process in which an initial recombination event is followed by a process of resolution, deleting extraneous sequences and optimizing viral fitness. This process has implications for our wider understanding of 'evolution by duplication' in the positive-strand RNA viruses.
Item Type: | Journal Article | ||||||||
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Subjects: | Q Science > QH Natural history > QH426 Genetics | ||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||
Library of Congress Subject Headings (LCSH): | Genetic recombination, Enteroviruses -- Genetics | ||||||||
Journal or Publication Title: | PLoS Pathogens | ||||||||
Publisher: | Public Library of Science | ||||||||
ISSN: | 1553-7374 | ||||||||
Official Date: | 12 June 2014 | ||||||||
Dates: |
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Volume: | Volume 10 | ||||||||
Number: | Number 6 | ||||||||
Article Number: | Article number e1004191 | ||||||||
DOI: | 10.1371/journal.ppat.1004191 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||
Date of first compliant deposit: | 28 December 2015 | ||||||||
Date of first compliant Open Access: | 28 December 2015 | ||||||||
Funder: | University of Warwick, Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Medical Research Council (Great Britain) (MRC) | ||||||||
Grant number: | G0401584 (MRC), G1100139 (MRC) |
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