Group Selection and Contribution of Minority Variants during Virus Adaptation Determines Virus Fitness and Phenotype

Abstract

Understanding how a pathogen colonizes and adapts to a new host environment is a primary aim in studying emerging infectious diseases. Adaptive mutations arise among the thousands of variants generated during RNA virus infection, and identifying these variants will shed light onto how changes in tropism and species jumps can occur. Here, we adapted Coxsackie virus B3 to a highly permissive and less permissive environment. Using deep sequencing and bioinformatics, we identified a multi-step adaptive process to adaptation involving residues in the receptor footprints that correlated with receptor availability and with increase in virus fitness in an environment-specific manner. We show that adaptation occurs by selection of a dominant mutation followed by group selection of minority variants that together, confer the fitness increase observed in the population, rather than selection of a single dominant genotype.

Lipid Tales of Viral Replication and Transmission

“…Even small genetic differences among quasispecies can manifest themselves, in the next infection cycle, in differing rates of RNA translation, RNA synthesis, particle assembly, resistance to innate immune defenses, etc. [97,98]. While these mutations might determine the replicative fate of viral particle infecting a cell alone, delivered in a vesicle as part of a population, cooperative interactions among quasispecies including sharing genetic templates, replication machinery, structural proteins and innate immune defense modulators, could yield greater overall survival and long term fitness for these genomes [98] ( Figure 2 ).…”

Extracellular vesicles are the Trojan horses of viral infection

“…This brings up the intriguing possibility that vesicular travel of viral populations may be nature's way of generating high multiplicities of infection in order to enhance viral propagation and survival [33]. In particular for RNA viruses, having a high multiplicity of infection can provide greater opportunities for genetic cooperativity [34•,35•]. Because of rapid replication kinetics combined with an inability to correct errors generated by their own RNA dependent RNA polymerases, the population of RNA viruses within a cell are not identical and instead are a mix of ‘quasispecies’.…”

Within Host Evolution Selects for a Dominant Genotype of Mycobacterium tuberculosis while T Cells Increase Pathogen Genetic Diversity

“…The severe nature of bottlenecks implies that the success of infection depends on 1) the genetic diversity of the pathogen population in the donor host and, 2) the selection of adapted genotypes during transmission. For HIV and other RNA viruses, founder particles are biased to favor the transmission of variants associated with increased fitness[3, 4]. The corresponding increase in fitness results from the selection and contribution of low frequency variants, and not to the effect of a single, dominant genome.…”