Antiviral Strategies Based on Lethal Mutagenesis and Error Threshold
The concept of error threshold derived from quasispecies theory is at the basis of lethal mutagenesis, a new antiviral strategy based on the increase of virus mutation rate above an extinction threshold. Research on this strategy is justified by several inhibitor-escape routes that viruses utilize to ensure their survival. Successive steps in the transition from an organized viral quasispecies into loss of biologically meaningful genomic sequences are dissected. The possible connections between theoretical models and experimental observations on lethal mutagenesis are reviewed. The possibility of using combination of virus-specific mutagenic nucleotide analogues and broad-spectrum, non-mutagenic inhibitors is evaluated. We emphasize the power that quasispecies theory has had to stimulate exploration of new means to combat pathogenic viruses.
KeywordsMutagenic Agent Fitness Landscape Mutant Spectrum Error Threshold Progeny Production
We are indebted to many colleagues in our laboratory for their contributions to quasispecies investigation, as reflected in the reference list. Work supported by grants BFU2011-23604 and SAF2014-52400-R from Spanish Ministries, and S2013/ABI-2906 (PLATESA) from Comunidad Autónoma de Madrid and Fundación Ramón Areces. CIBERehd (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas) is funded by Instituto de Salud Carlos III. C.P. is supported by the Miguel Servet program of the Instituto de Salud Carlos III (CP14/00121).
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