Abstract

Viral quasispecies are dynamic distributions of nonidentical but closely related mutant and recombinant viral genomes subjected to a continuous process of genetic variation, competition, and selection that may act as a unit of selection. The quasispecies concept owes its theoretical origins to a model for the origin of life as a collection of mutant RNA replicators. Independently, experimental evidence for the quasispecies concept was obtained from sampling of bacteriophage clones, which revealed that the viral populations consisted of many mutant genomes whose frequency varied with time of replication. Similar findings were made in animal and plant RNA viruses. Quasispecies became a theoretical framework to understand viral population dynamics and adaptability. The evidence came at a time when mutations were considered rare events in genetics, a perception that was to change dramatically in subsequent decades. Indeed, viral quasispecies was the conceptual forefront of a remarkable degree of biological diversity, now evident for cell populations and organisms, not only for viruses. Quasispecies dynamics unveiled complexities in the behavior of viral populations,with consequences for disease mechanisms and control strategies. This review addresses the origin of the quasispecies concept, its major implications on both viral evolution and antiviral strategies, and current and future prospects.

Highlights

  • In virology, quasispecies is defined as the set of mutant genomes that comprise viral populations

  • The present-day scenario is in sharp contrast with concepts of mutational stasis that prevailed in genetics well into the twentieth century

  • Quasispecies dynamics has provided a molecular interpretation of why some vaccine and antiviral therapeutics fail and has suggested new approaches for viral disease prevention and treatment. Among the latter is lethal mutagenesis—virus extinction by an externally induced excess of mutations—which has acquired new impetus with the need to respond to the coronavirus disease 2019 (COVID-19) emergence (Sections 9 and 10)

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Summary

INTRODUCTION

Quasispecies is defined as the set of mutant genomes that comprise viral populations. Mutant distributions offer an interpretation of adaptation based on the dynamic replacement of genome subpopulations within replicating ensembles. This is not a minor facet because responding to harsh selective constraints or to subtle environmental changes is what viruses have to do most of the time, including when they spread within organisms to cause disease. Quasispecies dynamics has provided a molecular interpretation of why some vaccine and antiviral therapeutics fail and has suggested new approaches for viral disease prevention and treatment. Among the latter is lethal mutagenesis—virus extinction by an externally induced excess of mutations—which has acquired new impetus with the need to respond to the coronavirus disease 2019 (COVID-19) emergence (Sections 9 and 10). Following the account of the origin of quasispecies, we recapitulate its major implications for virology as we perceive them half a century later

ORIGIN OF QUASISPECIES THEORY
EXPERIMENTAL ORIGIN OF QUASISPECIES
OVERVIEW OF QUASISPECIES IMPACT FOR VIROLOGY
MUTANT SPECTRA AS PHENOTYPIC RESERVOIRS
A PERMANENT POPULATION DISEQUILIBRIUM
THE ELUSIVE MEANING OF CONSERVATION
IMPACT ON ANTIVIRAL STRATEGIES
10. ANY LESSONS FOR COVID-19?
11. CLOSING STATEMENTS
SUMMARY POINTS
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