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

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Schmidt-Martin, Daniel
Crosbie, Orla
Kenny-Walsh, Elizabeth
Fanning, Liam J.
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Dove Press
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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.
Fitness landscapes , Adaptation , Evolution , Quasispecies , Replicative homeostasis
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
© 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.