Viral Transmission Dynamics at Single-Cell Resolution Reveal Transiently Immune Subpopulations Caused by a Carrier State Association

Monitoring the complex transmission dynamics of a bacterial virus (temperate phage P22) throughout a population of its host (Salmonella Typhimurium) at single cell resolution revealed the unexpected existence of a transiently immune subpopulation of host cells that emerged from peculiarities preceding the process of lysogenization. More specifically, an infection event ultimately leading to a lysogen first yielded a phage carrier cell harboring a polarly tethered P22 episome. Upon subsequent division, the daughter cell inheriting this episome became lysogenized by an integration event yielding a prophage, while the other daughter cell became P22-free. However, since the phage carrier cell was shown to overproduce immunity factors that are cytoplasmically inherited by the P22-free daughter cell and further passed down to its siblings, a transiently resistant subpopulation was generated that upon dilution of these immunity factors again became susceptible to P22 infection. The iterative emergence and infection of transiently resistant subpopulations suggests a new bet-hedging strategy by which viruses could manage to sustain both vertical and horizontal transmission routes throughout an infected population without compromising a stable co-existence with their host.

本研究以单细胞分辨率监测了宿主——鼠伤寒沙门氏菌（Salmonella Typhimurium）种群中细菌病毒温和噬菌体P22（temperate phage P22）的复杂传播动力学，意外揭示了一类由溶原化进程前期特殊机制催生的瞬时免疫宿主亚群。具体而言，最终导向溶原化的感染事件会首先产生一株携带极性锚定P22附加体的噬菌体携带细胞。该细胞完成后续分裂时，继承该附加体的子细胞会通过整合事件发生溶原化，形成原噬菌体（prophage），而另一子细胞则不携带P22。然而研究显示，噬菌体携带细胞会过量表达免疫因子；这类因子经细胞质遗传传递给无P22的子细胞，并进一步传递至其子代，由此形成瞬时抗性亚群。当这些免疫因子被稀释后，该亚群会再度对P22感染易感。瞬时抗性亚群的反复出现与感染现象，提示了一种全新的风险对冲策略（bet-hedging strategy）：病毒可通过该策略在受感染种群中同时维持垂直传播与水平传播路径，且不会破坏与宿主的稳定共存关系。