Data from: Evolution of increased survival in RNA viruses specialized on cancer-derived cells

Viruses and other pathogens can diverge in their evolved host-use strategies, due to exposure to different host types and conflicts between within-host reproduction and between-host survival. Most host-pathogen studies have emphasized the role of intra-host reproduction in the evolution of pathogen virulence, whereas the role of extra-host survival has received less attention. Here we examined 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, non-cancerous cells, or alternating passages of the two host types. We observed that free-living survival improved when VSV populations specialized on human cancer-derived (HeLa) cells, whereas this trait was not associated with selection on non-cancer 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 in between host-cell replenishment. We also showed evidence that increases in virion survival were associated with decreases in virulence, suggesting 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.病毒及其他病原体因接触不同宿主类型，以及宿主体内繁殖与宿主体间存活间的演化冲突，会在宿主利用策略上出现分化。绝大多数宿主-病原体相关研究均聚焦于宿主体内繁殖在病原体毒力演化中的作用，而宿主体外存活的相关作用则较少受到关注。本研究针对宿主使用历史存在差异的RNA病毒种群，探究了其自由存活病毒粒子（free-living virion）的演化规律。为此，我们采用了水泡性口炎病毒（vesicular stomatitis virus, VSV）的多个谱系，这些谱系在实验室组织培养体系中分别以癌细胞系、非癌细胞系，或两种宿主类型交替传代的方式进行了100代的实验演化。我们观察到，当VSV种群专性适应人类癌细胞系（海拉细胞, HeLa）时，其自由存活能力显著提升；而该性状与非癌细胞系或两种细胞类型组合的选择压力并无关联。我们将该结果归因于海拉细胞单层培养物的存活周期更短，以及组织培养中病毒在海拉细胞上的快速细胞间扩散——这两种因素均可能在宿主细胞更替过程中，筛选出稳定性更强的病毒粒子。本研究还证实，病毒粒子存活能力的提升与毒力下降存在关联，这表明在单一细胞类型上培养的VSV种群，其存活能力与毒力之间存在演化权衡（trade-off）。本研究结果为RNA病毒"sit and wait"感染策略的成因与后果提供了新的见解。