Probabilistic bet hedging, a strategy to maximize fitness in unpredictable environments by matching phenotypic variability to environmental variability, is theorized to account for the evolution of various fate-specification decisions, including viral latency. However, the molecular mechanisms underlying bet hedging remain unclear. Here, we report that large variability in protein abundance within individual herpesvirus virion particles enables probabilistic bet hedging between viral replication and latency. Superresolution imaging of individual virions of the human herpesvirus cytomegalovirus (CMV) showed that virion-to-virion levels of pp71 tegument protein—the major viral transactivator protein—exhibit extreme variability. This super-Poissonian tegument variability promoted alternate replicative strategies: high virion pp71 levels enhance viral replicative fitness but, strikingly, impede silencing, whereas low virion pp71 levels reduce fitness but promote silencing. Overall, the results indicate that stochastic tegument packaging provides a mechanism enabling probabilistic bet hedging between viral replication and latency.

概率赌注对冲是一种通过将表型变异性与环境变异性相匹配来最大化在不可预测环境中的适应度的策略，理论上可以解释各种命运规范决策的演变，包括病毒潜伏期。然而，押注对冲的分子机制仍不清楚。在这里，我们报告了单个疱疹病毒病毒粒子内蛋白质丰度的巨大变异性，使得病毒复制和潜伏期之间的概率赌注成为可能。人类疱疹病毒巨细胞病毒 (CMV) 的单个病毒粒子的超分辨率成像显示，pp71 外膜蛋白（主要的病毒反式激活蛋白）的病毒粒子与病毒粒子水平表现出极大的变异性。这种超泊松外皮变异性促进了交替的复制策略：高病毒粒子 pp71 水平增强病毒复制适应性，但显着地阻碍沉默，而低病毒粒子 pp71 水平降低适应性但促进沉默。总体而言，结果表明随机外皮包装提供了一种机制，能够在病毒复制和潜伏期之间进行概率赌注对冲。