Future prospects for the treatment of rapidly evolving viral pathogens: insights from evolutionary biology

Abstract

The evolutionary dynamics of viruses must be taken into consideration in designing preventive and therapeutic treatments. Here we review mechanisms by which viruses adapt in response to antiviral interventions. We propose combination therapy and multiepitopic vaccines as adequate to circumvent virus adaptability. An alternative design, termed lethal mutagenesis or virus entry into error catastrophe is presented. It exploits the high error rates inherent in RNA virus replication, to provoke virus extinction through excess of mutations.

Keywords::

• antiviral agents
• escape mutants
• fitness landscape
• hepatitis C virus
• human immunodeficiency virus
• lethal mutagenesis
• nucleoside analogs
• quasispecies dynamics
• RNA viruses

Acknowledgements

We are indebted to JC de la Torre for collaboration, and to M Dávila and AI de Ávila for technical assistance.