RNA Viruses: Control, Mutagenesis and Extinction

Abstract

Ribonucleic acid (RNA) viruses form populations with a high degree of genetic diversity, which facilitates adaptation to most changes in the environmental conditions. Therapeutic treatments are a type of change in the selective pressures to which RNA viruses also try to adapt. The selection of drug‐resistant mutants and escape mutants able to evade the immune response of the host are clear examples of the capacity of RNA viruses to maintain their infectivity in the presence of inhibitors. Therefore, it is increasingly evident that to find successful control measures for RNA viruses it is necessary to take into account the adaptive potential of these pathogens. Combination therapies and multiepitopic vaccines are antiviral strategies that have demonstrated their effectiveness. Another promising approach, referred to as lethal mutagenesis, exploits the high error rates of RNA viruses to push them above an error threshold incompatible with viability.

Key Concepts:

  • RNA viruses cause diseases that can be very difficult to treat.

  • RNA viruses replicate their genomes with a very high error rate, giving rise to populations that contain a large genetic diversity.

  • RNA viruses possess a great adaptive capacity that permits them to rapidly generate drug‐resistant mutants, as well as antibody or cytotoxic T lymphocyte escape mutants.

  • The development of strategies for the control of RNA viruses must take into account their adaptive potential.

  • One of the most successful strategies to control RNA viruses is the use of combination therapies.

  • Lethal mutagenesis is a new antiviral therapy, which consists in the artificial increase of the virus error rate above a limit that is incompatible with viability.

Keywords: RNA viruses; extinction; quasispecies; adaptation; selection; antiviral drugs; lethal mutagenesis; combination therapy; drug‐resistant mutant

Figure 1.

Structure of RNA virus populations. The lines represent the genomes of individual viruses. Coloured letters are mutations relative to the consensus sequence, which is obtained through nucleotide sequencing and represents the most frequent nucleotide at each genomic position in the ensemble of genomes. The master sequence corresponds to the highest fitness genome.

Figure 2.

Scheme showing the opposing consequences that the increase of the error rate has in viral populations. The population would be extinguished or adapted to replicate at increased error rate depending on whether the benefits provided by the increased adaptive capacity outweigh the negative consequences of the fitness decrease.

Figure 3.

Distribution of genomes composing a theoretical quasispecies in a fitness landscape below and above the error threshold.

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How to Cite close
Lázaro, Ester(Jun 2011) RNA Viruses: Control, Mutagenesis and Extinction. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0023276]