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暴露于不同宿主类型，以及宿主体内繁殖与跨宿主存活之间的冲突，其演化出的宿主利用策略会产生分化。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，而跨宿主存活的相关功能则较少受到关注。本研究针对宿主利用历史存在差异的RNA病毒种群，探究了其游离病毒粒子存活能力的演化规律。为此，我们以水疱性口炎病毒（vesicular stomatitis virus, VSV）的多个谱系为研究对象，这些谱系通过实验室组织培养实验完成演化：分别在癌源细胞、非癌源细胞，或两种宿主类型交替传代的条件下培养100代。我们观察到，当VSV种群专性适应人类癌源（HeLa）细胞时，其游离病毒粒子存活能力得到提升；而当选择压力作用于非癌源细胞或两种细胞的组合时，该性状并未出现显著变化。我们将该发现归因于两点：一是HeLa细胞单层的存活周期更短，二是组织培养中病毒在HeLa细胞上的细胞间传播速度更快——这两种因素均可能在宿主细胞更替期间，对病毒提升稳定性产生选择压力。本研究还提供了证据表明，病毒粒子存活能力的提升与毒力下降存在关联，这表明在单一宿主细胞类型下培养的VSV种群，其存活能力与毒力之间存在演化权衡。本研究结果为RNA病毒‘静待宿主（sit and wait）’感染策略的成因与后果提供了全新的视角。