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Quasispecies and Drug Resistance

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Handbook of Antimicrobial Resistance

Abstract

Mutant spectra of viral quasispecies are complex reservoirs of genetic and phenotypic variants, including drug-resistant mutants. Here we review basic features of RNA viral quasispecies such as internal interactions within mutant spectra and the effect of population size and bottleneck events as they affect the frequency of inhibitor-escape mutants. Genetic barriers to resistance and fitness cost of specific amino acid substitutions involved in resistance are discussed, with specific examples for human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV). Prospects for new antiviral designs aimed at counteracting the adaptive potential of viral quasispecies are presented.

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Acknowledgments

Work at Centro de Biología Molecular Severo Ochoa (CSIC-UAM) supported by grant BFU2011-23604 and Fundación Ramón Areces. N.M.B. is supported by a JAE-DOC contract from Consejo Superior de Investigaciones Científicas (CSIC) and J.S. by a Juan de la Cierva contract from CSIC. CIBERehd is funded by Instituto de Salud Carlos III. Work in the lab of Dr. Menéndez-Arias was supported in part by grants of the Spanish Ministries of Economy and Competitiveness (BIO2010/15542 and BIO2013-48788-C2-1-R) and Health, Social Services and Equality (EC11-025).

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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, Ana M. Ortega-Prieto, Nathan M. Beach, Julie Sheldon, Luis Menéndez-Arias & Esteban Domingo

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

    Celia Perales & Esteban Domingo

  3. Division of Experimental Virology, Twincore, Centre for Experimental and Clinical Infection Research, a joint venture between Medical School Hannover and Helmholtz Centre for Infection Research, Hannover, Germany

    Julie Sheldon

Authors
  1. Celia Perales
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  2. Ana M. Ortega-Prieto
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  3. Nathan M. Beach
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  4. Julie Sheldon
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  5. Luis Menéndez-Arias
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  6. Esteban Domingo
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Corresponding author

Correspondence to Celia Perales .

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Editors and Affiliations

  1. Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada

    Albert Berghuis

  2. Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada

    Greg Matlashewski

  3. Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada

    Mark A. Wainberg

  4. Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada

    Donald Sheppard

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© 2017 Springer Science+Business Media New York

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Perales, C., Ortega-Prieto, A.M., Beach, N.M., Sheldon, J., Menéndez-Arias, L., Domingo, E. (2017). Quasispecies and Drug Resistance. In: Berghuis, A., Matlashewski, G., Wainberg, M., Sheppard, D. (eds) Handbook of Antimicrobial Resistance. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0694-9_1

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