Departments of Mathematics and Biology & York Cross-Disciplinary Centre for Systems Analysis, University of York, York, UK.
Division of Infection and Immunity, University College London, Gower Street, London WC1E 6BT, UK.
Trends Microbiol. 2024 Jan;32(1):17-26. doi: 10.1016/j.tim.2023.07.003. Epub 2023 Jul 27.
The recent revolution in imaging techniques and results from RNA footprinting in situ reveal how the bacteriophage MS2 genome regulates both particle assembly and genome release. We have proposed a model in which multiple packaging signal (PS) RNA-coat protein (CP) contacts orchestrate different stages of a viral life cycle. Programmed formation and release of specific PS contacts with CP regulates viral particle assembly and genome uncoating during cell entry. We hypothesize that molecular frustration, a concept introduced to understand protein folding, can be used to better rationalize how PSs function in both particle assembly and genome release. More broadly this concept may explain the directionality of viral life cycles, for example, the roles of host cofactors in HIV infection. We propose that this is a universal principle in virology that explains mechanisms of host-virus interaction and suggests diverse therapeutic interventions.
最近成像技术的发展以及 RNA 足迹原位技术的结果揭示了噬菌体 MS2 基因组如何调控颗粒组装和基因组释放。我们提出了一个模型，其中多个包装信号（PS）RNA-外壳蛋白（CP）接触协调病毒生命周期的不同阶段。CP 与 PS 的特定接触的有组织形成和释放调节了细胞进入时病毒颗粒的组装和基因组脱壳。我们假设，分子受挫（frustration），一个被引入来理解蛋白质折叠的概念，可以用来更好地说明 PS 在颗粒组装和基因组释放中的作用。更广泛地说，这个概念可以解释病毒生命周期的方向性，例如，宿主辅助因子在 HIV 感染中的作用。我们提出，这是病毒学中的一个普遍原则，它解释了宿主-病毒相互作用的机制，并提出了多种治疗干预措施。
