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Antiviral Strategies Based on Lethal Mutagenesis and Error Threshold

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Quasispecies: From Theory to Experimental Systems

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 392))

Abstract

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.

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Acknowledgments

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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Authors and Affiliations

  1. Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049, Madrid, Spain

    Celia Perales & Esteban Domingo

  2. Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain

    Celia Perales & Esteban Domingo

  3. Liver Unit, Internal Medicine, Laboratori of Malalties Hepàtiques, Vall d’Hebron Institut de Recerca-Hospital Universitari Vall d’Hebron, Universitat Autonoma de Barcelona, 08035, Barcelona, Spain

    Celia Perales

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  1. Celia Perales
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  2. Esteban Domingo
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Correspondence to Esteban Domingo .

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Editors and Affiliations

  1. Campus de Cantoblanco, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain

    Esteban Domingo

  2. The Santa Fe Institute, Santa Fe, NM, USA and Institut f. Theoretische Chemie, Universität Wien, Vienna, Austria

    Peter Schuster

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Perales, C., Domingo, E. (2015). Antiviral Strategies Based on Lethal Mutagenesis and Error Threshold. In: Domingo, E., Schuster, P. (eds) Quasispecies: From Theory to Experimental Systems. Current Topics in Microbiology and Immunology, vol 392. Springer, Cham. https://doi.org/10.1007/82_2015_459

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