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

Schmidt-Martin, Daniel; Crosbie, Orla; Kenny-Walsh, Elizabeth; Fanning, Liam J.

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

Files

HCV_VARIABLE_DS.pdf(374.08 KB)

Published Version

Date

2012

Authors

Schmidt-Martin, Daniel

Crosbie, Orla

Kenny-Walsh, Elizabeth

Fanning, Liam J.

Publisher

Dove Press

Published Version

10.2147/VAAT.S31785

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.

Keywords

Fitness landscapes , Adaptation , Evolution , Quasispecies , Replicative homeostasis

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