Month: September 2022

UNIT OF SELECTION. "The evidence just summarized is consistent with the idea that viral quasispecies can act as a unit of selection, group selection, one of the features of complex systems in the sense that the properties of the “whole” cannot be directly inferred from the properties of the “individuals”. Viral quasispecies have approached virology to the growing field of biological complexity." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

"FITNESS, defined as the overall capacity of a virus to produce infectious progeny has long been recognized as a critical parameter that reflects virus adaptation to a specific environment. Unperturbed replication of large viral populations in a constant environment results in fitness gain, adaptation, while repeated bottlenecks that result in accumulation of mutations result in fitness decrease, de-adaptation." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

DRUG RESISTANCE. "One of the conclusions of these studies is that replicative fitness can be an independent predictor of the response of HCV to inhibitors used in therapy. It is known that viruses never exposed to inhibitors can nevertheless include in their mutant spectra mutations that confer resistance to the inhibitors." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

RESISTANCE PHENOTYPES. “In the studies with HCV it was important to exclude that inhibitor resistance mutations had not been acquired as a consequence of fitness gain. This possibility was excluded not only by NGS but also by the multiplicity of infection (MOI)-independent kinetics of virus production in the presence of inhibitors, and the maintenance of the resistance phenotype in biological clones of the passaged populations." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

PROGNOSTIC FITNESS. "Translated into clinical practice, it means that the evolutionary history of HCV in infected patients may influence the response to treatments. In particular, long-term replication of HCV during prolonged chronicity may increase viral fitness to the detriment of treatment efficacy, as observed in clinical practice. These observations render essential to develop methods to define fitness values in vivo and to explore the fitness landscape in viral populations." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

DIAGNOSTIC CHALLENGES. "Characterizing the genetic structure of virus populations remains a fundamental challenge. High-throughput sequencing technologies are capable of generating very large datasets; but distinguishing true genetic variation from sequencing error remains a central problem due to the high average sequencing error rates for NGS and given that even small error probabilities result in a significant number of sequencing errors." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

DIAGNOSTIC SOLUTION. "To overcome this limitation an experimental approach was developed that dramatically reduces sequencing errors.The basic premise of this method, called Circular Sequencing (or CirSeq). Using this approach, we are now able to estimate changes in mutation frequency of variants that exist in the population at very low levels. This opens an opportunity to determine fitness landscape at single nucleotide resolution." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

LOW FIDELITY. "The focus on mutation as a driving force in viral evolution has tended to overlook the tremendous cost of low replicative fidelity." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

POPULATION SHIELD. "Most mutations have deleterious effects on viral fitness. Tolerance to mutational load determines the nature and extent of genetic diversity that can be maintained in the population. Thus, viral population diversity results from both the generation of mutations and the tolerance to them; these two factors together drive adaptation and virus evolution." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

COMPLEMENTATION. "The efficiency of purifying (or negative) selection is the product of effective population size and the average mutational fitness effect(s). In large populations, strong selection will quickly purge mutants with lower fitness. Larger population sizes may also result in higher multiplicities of infection, where a given cell supports replication of at least two different genomes. Here, genetic complementation can increase the robustness of the viral population." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn