RT Journal Article
T1 Extinction of hepatitis C virus by ribavirin in hepatoma cells involves lethal mutagenesis
A1 Ortega-Prieto, Ana María
A1 Sheldon, Julie
A1 Grande-Pérez, Ana
A1 Tejero, Hector
A1 Gregori, Josep
A1 Quer, Josep
A1 Esteban, Juan I.
A1 Domingo, Esteban
A1 Perales, Celia
K1 Virus de la hepatitis C
AB Lethal mutagenesis, or virus extinction produced by enhanced mutation rates, is under investigation as an antiviral strategy that aims at counteracting the adaptive capacity of viral quasispecies, and avoiding selection of antiviral-escape mutants. To explore lethal mutagenesis of hepatitis C virus (HCV), it is important to establish whether ribavirin, the purine nucleoside analogue used in anti-HCV therapy, acts as a mutagenic agent during virus replication in cell culture. Here we report the effect of ribavirin during serial passages of HCV in human hepatoma Huh-7.5 cells, regarding viral progeny production and complexity of mutant spectra. Ribavirin produced an increase of mutant spectrum complexity and of the transition types associated with ribavirin mutagenesis, resulting in HCV extinction. Ribavirin-mediated depletion of intracellular GTP was not the major contributory factor to mutagenesis since mycophenolic acid evoked a similar decrease in GTP without an increase in mutant spectrum complexity. The intracellular concentration of the other nucleoside-triphosphates was elevated as a result of ribavirin treatment. Mycophenolic acid extinguished HCV without an intervening mutagenic activity. Ribavirin-mediated, but not mycophenolic acid-mediated, extinction of HCV occurred via a decrease of specific infectivity, a feature typical of lethal mutagenesis. We discuss some possibilities to explain disparate results on ribavirin mutagenesis of HCV.
PB PLOS One
YR 2013
FD 2013-08
LK https://hdl.handle.net/10630/35340
UL https://hdl.handle.net/10630/35340
LA eng
NO Ortega-Prieto AM, Sheldon J, Grande-Pérez A, Tejero H, Gregori J, Quer J, et al. (2013) Extinction of Hepatitis C Virus by Ribavirin in Hepatoma Cells Involves Lethal Mutagenesis. PLoS ONE 8(8): e71039. https://doi.org/10.1371/journal.pone.0071039
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 22 ene 2026