Lethal Mutagenesis of Foot-and-Mouth Disease Virus Involves Shifts in Sequence Space
- 1 December 2011
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 85 (23), 12227-12240
- https://doi.org/10.1128/jvi.00716-11
Abstract
Lethal mutagenesis or virus transition into error catastrophe is an antiviral strategy that aims at extinguishing a virus by increasing the viral mutation rates during replication. The molecular basis of lethal mutagenesis is largely unknown. Previous studies showed that a critical substitution in the foot-and-mouth disease virus (FMDV) polymerase was sufficient to allow the virus to escape extinction through modulation of the transition types induced by the purine nucleoside analogue ribavirin. This substitution was not detected in mutant spectra of FMDV populations that had not replicated in the presence of ribavirin, using standard molecular cloning and nucleotide sequencing. Here we selectively amplify and analyze low-melting-temperature cDNA duplexes copied from FMDV genome populations passaged in the absence or presence of ribovirin Hypermutated genomes with high frequencies of A and U were present in both ribavirin -treated and untreated populations, but the major effect of ribavirin mutagenesis was to accelerate the occurrence of AU-rich mutant clouds during the early replication rounds of the virus. The standard FMDV quasispecies passaged in the absence of ribavirin included the salient transition-modulating, ribavirin resistance mutation, whose frequency increased in populations treated with ribavirin. Thus, even nonmutagenized FMDV quasispecies include a deep, mutationally biased portion of sequence space, in support of the view that the virus replicates close to the error threshold for maintenance of genetic information.This publication has 87 references indexed in Scilit:
- Somatic hypermutation of human mitochondrial and nuclear DNA by APOBEC3 cytidine deaminases, a pathway for DNA catabolismProceedings of the National Academy of Sciences, 2011
- Error correction of next-generation sequencing data and reliable estimation of HIV quasispeciesNucleic Acids Research, 2010
- Competition-colonization dynamics in an RNA virusProceedings of the National Academy of Sciences of the United States of America, 2010
- Biological Effect of Muller's Ratchet: Distant Capsid Site Can Affect Picornavirus Protein ProcessingJournal of Virology, 2009
- The 30th anniversary of quasispeciesEMBO Reports, 2009
- Naturally occurring dominant resistance mutations to hepatitis C virus protease and polymerase inhibitors in treatment-naïve patientsHepatology, 2008
- Evidence for Editing of Human Papillomavirus DNA by APOBEC3 in Benign and Precancerous LesionsScience, 2008
- Guinea Pig-Adapted Foot-and-Mouth Disease Virus with Altered Receptor Recognition Can Productively Infect a Natural HostJournal of Virology, 2007
- Theory of Lethal Mutagenesis for VirusesJournal of Virology, 2007
- Foot-and-Mouth Disease Virus Mutant with Decreased Sensitivity to Ribavirin: Implications for Error CatastropheJournal of Virology, 2007