Hepatitis C quasispecies adaptation in the setting of a variable fidelity polymerase

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dc.contributor.author Schmidt-Martin, Daniel
dc.contributor.author Crosbie, Orla
dc.contributor.author Kenny-Walsh, Elizabeth
dc.contributor.author Fanning, Liam J.
dc.date.accessioned 2013-02-11T11:14:40Z
dc.date.available 2013-02-11T11:14:40Z
dc.date.copyright 2012
dc.date.issued 2012
dc.identifier.citation Schmidt-Martin D, Crosbie O, Kenny-Walsh E, Fanning LJ (2012) 'Hepatitis C quasispecies adaptation in the setting of a variable fidelity polymerase'. Journal of Virus Adaptation and Treatment, 4 (1):43-50. doi: 10.2147/VAAT.S31785 en
dc.identifier.volume 4 en
dc.identifier.issued 1 en
dc.identifier.startpage 43 en
dc.identifier.endpage 50 en
dc.identifier.uri http://hdl.handle.net/10468/960
dc.identifier.doi 10.2147/VAAT.S31785
dc.description.abstract Hepatitis C (HCV) is a virus characterized by an RNA-dependent RNA polymerase that lacks a proofreading mechanism and, as a result, generates a quasispecies. There is emerging evidence that this RNA-dependent RNA polymerase may in fact have variable fidelity. Here, we review the relevant concepts, including fitness landscapes, clonal interference, robustness, selection, adaptation, mutation rates, and their optimization, and provide a unique interpretation of a number of relevant theoretical models, evolving the theory of replicative homeostasis in light of their findings. We suggest that a variable fidelity polymerase can find its own optimal mutation rate, which is governed by the sequence itself and certain population dynamics. We propose that this concept can explain features of viral kinetics and clearance, both spontaneously and following treatment of chronic HCV. We point to evidence that supports this theory and explain how it refines replicative homeostasis and conclude by discussing particular areas of potential research that might augment our understanding of viral host interactions at an individual cellular level. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Dove Press en
dc.relation.uri http://www.dovepress.com/hepatitis-c-quasispecies-adaptation-in-the-setting-of-a-variable-fidel-peer-reviewed-article-VAAT
dc.rights © 2012 Schmidt-Martin et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. en
dc.subject Fitness landscapes en
dc.subject Adaptation en
dc.subject Evolution en
dc.subject Quasispecies en
dc.subject Replicative homeostasis en
dc.subject.lcsh Hepatitis C en
dc.title Hepatitis C quasispecies adaptation in the setting of a variable fidelity polymerase en
dc.type Article (peer-reviewed) en
dc.internal.authorurl http://www.ucc.ie/ga/meddept/Staff/DrLiamFanning/ en
dc.internal.authorcontactother Liam Fanning, Medicine Department, University College Cork, Cork, Ireland. +353-21-490-3000 Email: l.fanning@ucc.ie en
dc.internal.availability Full text available en
dc.date.updated 2013-01-18T14:59:46Z
dc.description.version Published Version en
dc.internal.rssid 192286580
dc.description.status Peer reviewed en
dc.identifier.journaltitle Journal of Virus Adaptation and Treatment en
dc.internal.copyrightchecked No - CORA - ROMEO and publisher's website. http://www.dovepress.com/author_guidelines.php?content_id=696 " Authors are also entitled to deposit the final electronic version of the article into an institutional or centrally organized subject repository upon publication." en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress l.fanning@ucc.ie en

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