Viral quasispecies

Abstract

Viral quasispecies refers to a population structure that consists of extremely large numbers of variant genomes, termed mutant spectra, mutant swarms or mutant clouds. Fueled by high mutation rates, mutants arise continually, and they change in relative frequency as viral replication proceeds. The term quasispecies was adopted from a theory of the origin of life in which primitive replicons) consisted of mutant distributions, as found experimentally with present day RNA viruses. The theory provided a new definition of wild type, and a conceptual framework for the interpretation of the adaptive potential of RNA viruses that contrasted with classical studies based on consensus sequences. Standard clonal analyses and deep sequencing methodologies have confirmed the presence of myriads of mutant genomes in viral populations, and their participation in adaptive processes. The quasispecies concept applies to any biological entity, but its impact is more evident when the genome size is limited and the mutation rate is high. This is the case of the RNA viruses, ubiquitous in our biosphere, and that comprise many important pathogens. In virology, quasispecies are defined as complex distributions of closely related variant genomes subjected to genetic variation, competition and selection, and that may act as a unit of selection. Despite being an integral part of their replication, high mutation rates have an upper limit compatible with inheritable information. Crossing such a limit leads to RNA virus extinction, a transition that is the basis of an antiviral design termed lethal mutagenesis.

The global population of SARS-CoV-2 is composed of six major subtypes

“…Populations of RNA viruses evolve rapidly due to their large population sizes, short generation times, and high mutation rates, this latter being a consequence of the RNA-dependent RNA polymerase (RdRP) which lacks the proofreading activity 7 . In fact, virus populations are composed of a broad spectrum of closely related genetic variants resembling one or more master sequences 8–10 . Mutation rates inferred for SARS-CoVs are considered moderate 11,12 due to the independent proofreading activity 13 .…”

Molecular basis of genetic variation of viruses

“…In an early study with the poliovirus RdRp in vitro, an increase in the error frequency was observed when the pH and Mg 2þ ion conditions were modified, and the decreased fidelity correlated with increased RNA elongation rate (Ward et al, 1988). A possible connection between elongation rate and copying fidelity cannot be ruled out, but current evidence points to template-copying fidelity as being the result of multiple factors, not necessarily linked to the rate of genome replication (Vignuzzi and Andino, 2010;Campagnola et al, 2015;Domingo and Perales, 2019).…”

2019 meeting of the global virus network

“…Step (ii) is guided by the multifactorial epidemiological fitness and transmission-associated random drift of genomes, and its description is based on phylodynamic approaches (Geoghegan and Holmes, 2018;Domingo and Perales, 2019). How events in step (i) influence events in step (ii) is an open question.…”