Quasispecies and drug 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.