Chapter 23 : Error Frequencies of Picornavirus RNA Polymerases: Evolutionary Implications for Virus Populations

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This chapter examines key features of the three main stages in virus evolution with examples drawn from several virus groups. It then reviews specific results with picornaviruses, as well as implications of high mutation rates and quasispecies dynamics for this important and diverse group of pathogens. With the levels of heterogeneity and viral load often seen in infected individuals, RNA virus populations include potentially all possible single mutants and decreasing amounts of multiple mutants. There are probably many routes to drug resistance, including amino acid replacements in the wall of the pocket preventing accommodation of the drug into the pocket (termed "exclusion" mutants), and replacements elsewhere in the capsid that affect viral uncoating. Resistant mutants display decreased affinity for the drug or increased affinity for the receptor, and often show low fitness values relative to their parental counterparts. Studies with picornaviral RNA-dependent RNA polymerases (replicases) face limitations derived from the difficulties in obtaining purified enzymes capable of sustaining multiple rounds of template-dependent copying. Viral quasispecies show features of complex adaptive systems such as mobilization of minority components (individual genomes from the mutant spectrum) in response to external stimuli. New developments in biochemistry and structural biology, and a deeper understanding of the principles governing viral evolution can now be combined to produce practical developments following an extensive (and necessary) accumulation of results from basic research.

Citation: Domingo E, Baranowski E, Escarmís C, Sobrino F, Holland J. 2002. Error Frequencies of Picornavirus RNA Polymerases: Evolutionary Implications for Virus Populations, p 285-298. In Semler B, Wimmer E (ed), Molecular Biology of Picornavirus. ASM Press, Washington, DC. doi: 10.1128/9781555817916.ch23

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Hepatitis C virus
Simian immunodeficiency virus
Foot-and-mouth disease virus
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