The role of environmental factors on the evolution of phenotypic diversity in vesicular stomatitis virus populations.

Virus adaptation to an ever-changing environment requires the availability of variants with phenotypes that can fulfil new requirements for replication. High mutation rates result in the generation of these variants. The factors that contribute to the maintenance or elimination of this diversity, however, are not fully understood. This study used a collection of vesicular stomatitis virus strains generated under different conditions to measure the extent of variation within each population, and tested the effects of several environmental factors on diversity. It was found that the host-cell type used for selection sometimes had an effect on the extent of variation and that there may be different levels of variation over time. Persistent infections promoted higher levels of diversity than acute infections, presumably due to complementation. In contrast, environmental heterogeneity, host breadth and the cell type used for testing (as opposed to the cell type used for selection) did not seem to have an effect on the amount of phenotypic diversity observed.

Genomic evolution of vesicular stomatitis virus strains with differences in adaptability.

Virus strains with a history of repeated genetic bottlenecks frequently show a diminished ability to adapt compared to strains that do not have such a history. These differences in adaptability suggest differences in either the rate at which beneficial mutations are produced, the effects of beneficial mutations, or both. We tested these possibilities by subjecting four populations (two controls and two mutants with lower adaptabilities) to multiple replicas of a regimen of positive selection and then determining the fitnesses of the progeny through time and the changes in the consensus, full-length sequences of 56 genomes. We observed that at a given number of passages, the overall fitness gains observed for control populations were larger than fitness gains in mutant populations. However, these changes did not correlate with differences in the numbers of mutations accumulated in the two types of genomes. This result is consistent with beneficial mutations having a lower beneficial effect on mutant strains. Despite the overall fitness differences, some replicas of one mutant strain at passage 50 showed fitness increases similar to those observed for the wild type. We hypothesized that these evolved, high-fitness mutants may have a lower robustness than evolved, high-fitness controls. Robustness is the ability of a virus to avoid phenotypic changes in the face of mutation. We confirmed our hypothesis in mutation-accumulation experiments that showed a normalized fitness loss that was significantly larger in mutant bottlenecked populations than in control populations.

Incongruent fitness landscapes, not tradeoffs, dominate the adaptation of vesicular stomatitis virus to novel host types.

Host radiation refers to the ability of parasites to adapt to new environments and expand or change their niches. Adaptation to one specific environment may involve a loss in adaptation to a second environment. Thus, fitness costs may impose limits to niche expansion and constitute the cost of specialization. Several reports have addressed the cost of host radiation in vesicular stomatitis virus (VSV), but in some cases the experimental setup may have resulted in the overestimation of fitness costs. To clarify this issue, experiments were carried out in which a reference strain of VSV was allowed to adapt to HeLa, MDCK and BHK-21 cells, and to a regime of alternation between HeLa and Madin-Darby canine kidney (MDCK) cells. Measurement of viral fitness on each cell type showed that most virus populations behaved as generalists, and increased in fitness in all environments. Tradeoffs, where a fitness increase in one environment led to a fitness decrease in another environment, were rare. These results highlight the importance of using appropriate methods to measure fitness in evolved virus populations, and provide further support to a model of evolutionary dynamics in which costs due to incongruent landscapes provided by different environments are more common than tradeoffs.