Quasispecies and Drug Resistance
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.
KeywordsAntiviral therapy Drug resistance Genetic barrier Hepatitis C virus (HCV) Human immunodeficiency virus type 1 (HIV-1) Mutant spectrum Replication rate Viral fitness Viral load Viral quasispecies
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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