Getting to Know Viral Evolutionary Strategies: Towards the Next Generation of Quasispecies Models

Abstract

Viral populations are formed by complex ensembles of genomes with broad phenotypic diversity. The adaptive strategies deployed by these ensembles are multiple and often cannot be predicted a priori. Our understanding of viral dynamics is mostly based on two kinds of empirical approaches: one directed towards characterizing molecular changes underlying fitness changes and another focused on population-level responses. Simultaneously, theoretical efforts are directed towards developing a formal picture of viral evolution by means of more realistic fitness landscapes and reliable population dynamics models. New technologies, chiefly the use of next-generation sequencing and related tools, are opening avenues connecting the molecular and the population levels. In the near future, we hope to be witnesses of an integration of these still decoupled approaches, leading into more accurate and realistic quasispecies models able to capture robust generalities and endowed with a satisfactory predictive power.

Internal Disequilibria and Phenotypic Diversification during Replication of Hepatitis C Virus in a Noncoevolving Cellular Environment

“…Fluctuations in infectivity were exhibited by FMDV clones that attained very low fitness values as a consequence of many serial plaque-to-plaque passages (55,56). In this case, fluctuations were attributed to the stochasticity caused by extreme bottlenecks, which resulted in high unpredictability of the fitness of the founder genome after each passage (14,57,58). In the current case, an alternation between dominance of interference (due to a transient increase of defective mutants) and complementation (known to occur within replicative units) may play a role (3,4,8,11,12,59).…”

The 5BSL3.2 Functional RNA Domain Connects Distant Regions in the Hepatitis C Virus Genome

“…The magnitude of the effect of the acquired mutations is dependent on the environment: changes can be favorable for the infection in a given host but may have important fitness costs in a different environment, even within the same infected individual. This phenomenon creates a complex picture for the prediction of the disease severity and impedes the development of novel therapies ( Manrubia and Lazaro, 2016 ; Perales and Domingo, 2016 ).…”