Evolution of Increased Survival in RNA Viruses Specialized on Cancer-Derived Cells

Abstract

Viruses and other pathogens can diverge in their evolved host-use strategies because of exposure to different host types and conflicts between within-host reproduction and between-host survival. Most host-pathogen studies have emphasized the role of intrahost reproduction in the evolution of pathogen virulence, whereas the role of extra-host survival has received less attention. Here, we examine the evolution of free-living virion survival in RNA virus populations differing in their histories of host use. To do so, we used lineages of vesicular stomatitis virus (VSV) that were experimentally evolved in laboratory tissue culture for 100 generations on cancer-derived cells, noncancerous cells, or alternating passages of the two host types. We observed that free-living survival improved when VSV populations specialized on human epithelial carcinoma (HeLa) cells, whereas this trait was not associated with selection on noncancer cells or combinations of the cell types. We attributed this finding to shorter-lived HeLa monolayers and/or rapid cell-to-cell spread of viruses on HeLa cells in tissue culture, both of which could select for enhanced virus stability between host-cell replenishment. We also showed evidence that increases in virion survival were associated with decreases in virulence, which suggests a trade-off between survival and virulence for the VSV populations on one cell type. Our results shed new light on the causes and consequences of "sit and wait" infection strategies in RNA viruses.

Pleiotropic Effects of Resistance-Breaking Mutations on Particle Stability Provide Insight into Life History Evolution of a Plant RNA Virus

“…Our results show that joint consideration of different life history traits is necessary for understanding virus evolution, as shown with experimental populations of phages or wild populations of avian influenza virus (56,71,72). The consequence of the reported pleiotropic effects of resistance-breaking mutations for the evolution of resistance-breaking is a complex one.…”

“…This result is consistent with previous ones, as data on the within-host fitness of some of the CP mutants analyzed here, reported by MorenoPérez et al (25), showed no correlation with our present stability data in different susceptible hosts (not shown). To our knowledge, the relationship between survival and multiplication has not been studied for other plant viruses, but studies with bacterial or animal-infecting viruses have demonstrated that such a trade-off is not general across systems (55)(56)(57)(58)(67)(68)(69)(70)(71)(72). Trade-offs between survival and reproduction, predicted by the life history theory, need not apply for viruses, because there is no obvious mechanistic reason to expect them due to the differences between the extracellular and intracellular environments where survival and reproduction, respectively, occur, as pointed out by Goldhill and Turner (19).…”

On the Biological Success of Viruses

“…Nevertheless, many types of abiotic perturbations can cause viral mortality, i.e., the inability of a viral particle to successfully complete within-host replication after experiencing an environmental challenge (56). A wide variety of environmental stressors are known to somehow compromise a virus's subsequent ability to productively infect a host; examples include changes in ambient temperature, ionic strength (saltiness), UV radiation, acidity, atmospheric pressure, and moisture (2,49,56,58). Although capsids function to protect viral nucleic acid from degradation by these and other environmental stressors, the protection is not absolute, and some viruses may experience very short half-lives outside of the host under these harsh conditions.…”

Delayed transmission selects for increased survival of vesicular stomatitis virus

“…Infectious viruses are nonmetabolizing microbes, which do not experience the metabolic trade‐offs sometimes suffered by cellular organisms. But it is evident that viruses experience life‐history compromises analogous to those observed in evolving populations of cellular life forms (e.g., De Paepe and Taddei ; Ogbunugafor et al ). The proteins and hereditary nucleic acids (RNA or DNA) of infectious virus particles may be easily degraded by extra‐host environmental stressors, such as extremes in temperature and pH.…”

“…The study showed that selection strictly on cancer cells led to increased extracellular survival of VSV populations, attributed to relatively faster cell‐to‐cell spread of viruses on cancer cells and the more rapid senescence of these cell types, either of which may select for enhanced virus stability between host‐cell replenishment. However, Ogbunugafor et al () showed only weak evidence that increased virion survival coincided with decreased intrahost reproduction, and this outcome was confounded by cell type (i.e., it was not observed across all host treatments), preventing the possibility of drawing general conclusions on evolved survival/reproduction trade‐offs in VSV.…”