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

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dc.contributor.authorSchmidt-Martin, Daniel
dc.contributor.authorCrosbie, Orla
dc.contributor.authorKenny-Walsh, Elizabeth
dc.contributor.authorFanning, Liam J.
dc.date.accessioned2013-02-11T11:14:40Z
dc.date.available2013-02-11T11:14:40Z
dc.date.copyright2012
dc.date.issued2012
dc.date.updated2013-01-18T14:59:46Z
dc.description.abstractHepatitis 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.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationSchmidt-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.S31785en
dc.identifier.doi10.2147/VAAT.S31785
dc.identifier.endpage50en
dc.identifier.issued1en
dc.identifier.journaltitleJournal of Virus Adaptation and Treatmenten
dc.identifier.startpage43en
dc.identifier.urihttps://hdl.handle.net/10468/960
dc.identifier.volume4en
dc.language.isoenen
dc.publisherDove Pressen
dc.relation.urihttp://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.subjectFitness landscapesen
dc.subjectAdaptationen
dc.subjectEvolutionen
dc.subjectQuasispeciesen
dc.subjectReplicative homeostasisen
dc.subject.lcshHepatitis Cen
dc.titleHepatitis C quasispecies adaptation in the setting of a variable fidelity polymeraseen
dc.typeArticle (peer-reviewed)en
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