Theoretical Models of Generalized Quasispecies

Wagner, Nathaniel; Atsmon-Raz, Yoav; Ashkenasy, Gonen

doi:10.1007/82_2015_456

Cited by 3 publications

(2 citation statements)

References 48 publications

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“…This and other repair activities, that may act on standard RNA or retroviral genomes [24–27], do not prevent the formation of mutant spectra, although their amplitude may be lower than for other RNA viruses, at least in populations close to a clonal (single genome) origin. Quasispecies dynamics will operate in any viral or cellular system in which due to high mutation rates (as a result of low fidelity nucleic acid polymerases or environmental alterations) mutant spectra are rapidly generated [16,28–32].…”

Section: Dynamic Heterogeneitymentioning

confidence: 99%

Viral quasispecies

2019

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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.

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Section: Dynamic Heterogeneitymentioning

confidence: 99%

Viral quasispecies

2019

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“…Additionally, it was found that different viruses within a quasispecies can exhibit a wide range of infectiousness, virulence, and replicative fitness [6,14,15]. Complementary to these developments, the theoretical foundations of quasispecies, proposed originally by Eigen, have been the subject of extensive study in mathematical biology and physics, leading to exact solution methods and applications ranging from B-cell receptor diversity to intra-tumor population dynamics [16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Modeling the dynamics of within-host viral infection and evolution predicts quasispecies distributions and phase boundaries separating distinct classes of infections

Lewis

Marshall

Jones

2021

Preprint

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We use computational modeling to study within-host viral infection and evolution. In our model, viruses exhibit variable binding to cells, with better infection and replication countered by a stronger immune response and a high rate of mutation. By varying host conditions (permissivity to viral entry T and immune clearance intensity A) for large numbers of cells and viruses, we study the dynamics of how viral populations evolve from initial infection to steady state and obtain a phase diagram of the range of cell and viral responses. We find three distinct replicative strategies corresponding to three physiological classes of viral infections: acute, chronic, and opportunistic. We show similarities between our findings and the behavior of real viral infections such as common flu, hepatitis, and SARS-CoV-2019. The phases associated with the three strategies are separated by a phase transition of primarily first order, in addition to a crossover region. Our simulations also reveal a wide range of physical phenomena, including metastable states, periodicity, and glassy dynamics. Lastly, our results suggest that the resolution of acute viral disease in patients whose immunity cannot be boosted can only be achieved by significant inhibition of viral infection and replication.

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Quasispecies and virus

Domingo

Perales

2018

Eur Biophys J

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Quasispecies theory has been instrumental in the understanding of RNA virus population dynamics because it considered for the first time mutation as an integral part of the replication process. The key influences of quasispecies theory on experimental virology have been: (1) to disclose the mutant spectrum nature of viral populations and to evaluate its consequences; (2) to unveil collective properties of genome ensembles that can render a mutant spectrum a unit of selection; and (3) to identify new vulnerability points of pathogenic RNA viruses on three fronts: the need to apply multiple selective constraints (in the form of drug combinations) to minimize selection of treatment-escape variants, to translate the error threshold concept into antiviral designs, and to construct attenuated vaccine viruses through alterations of viral polymerase copying fidelity or through displacements of viral genomes towards unfavorable regions of sequence space. These three major influences on the understanding of viral pathogens preceded extensions of quasispecies to non-viral systems such as bacterial and tumor cell collectivities and prions. These developments are summarized here.

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Theoretical Models of Generalized Quasispecies

Cited by 3 publications

References 48 publications

Viral quasispecies

Viral quasispecies

Modeling the dynamics of within-host viral infection and evolution predicts quasispecies distributions and phase boundaries separating distinct classes of infections

Quasispecies and virus

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