Simulation of the M13 life cycle II: Investigation of the control mechanisms of M13 infection and establishment of the carrier state.
Simulation of the M13 life cycle II: Investigation of the control mechanisms of M13 infection and establishment of the carrier state.
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M13生命周期模拟II：M13感染控制机制研究及载体状态建立。
DOI：
10.1016/j.virol.2016.08.015
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
J. D. Fisk
中科院分区：
文献类型：
--
作者：
Steven W Smeal;M. Schmitt;R. Pereira;A. Prasad;J. D. Fisk
噬菌体M13是一种真正的细菌寄生虫，能够吞噬被感染的细胞并控制许多细胞世代后代的产生。在这里，我们对M13的遗传结构模拟应用于定量分析宿主细胞环境与控制噬菌体生命周期的相互作用之间的相互作用，在感染的初始建立和跨多代细胞。多个模拟表明，噬菌体编码的反馈相互作用限制了宿主DNA聚合酶、RNA聚合酶和核糖体的利用。模拟揭示了p5翻译衰减在控制噬菌体双链DNA产生中的重要性，并提示p5翻译自衰减在资源分配中的作用未被充分认识。在单个世代中活跃的控制元件足以重现实验中观察到的噬菌体感染的多世代治愈。了解调控的微妙之处对于最大限度地利用M13颗粒作为纳米级器件的支架非常重要。
Bacteriophage M13 is a true parasite of bacteria, able to co-opt the infected cell and control the production of progeny across many cellular generations. Here, our genetically-structured simulation of M13 is applied to quantitatively dissect the interplay between the host cellular environment and the controlling interactions governing the phage life cycle during the initial establishment of infection and across multiple cell generations. Multiple simulations suggest that phage-encoded feedback interactions constrain the utilization of host DNA polymerase, RNA polymerase and ribosomes. The simulation reveals the importance of p5 translational attenuation in controlling the production of phage double-stranded DNA and suggests an underappreciated role for p5 translational self-attenuation in resource allocation. The control elements active in a single generation are sufficient to reproduce the experimentally-observed multigenerational curing of the phage infection. Understanding the subtleties of regulation will be important for maximally exploiting M13 particles as scaffolds for nanoscale devices.