Departments of Mathematics and Biology, and York Cross-disciplinary Centre for Systems Analysis, University of York, York YO10 5GE, United Kingdom; email:
Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom; email:
Annu Rev Biophys. 2019 May 6;48:495-514. doi: 10.1146/annurev-biophys-052118-115611. Epub 2019 Apr 5.
Viruses, entities composed of nucleic acids, proteins, and in some cases lipids lack the ability to replicate outside their target cells. Their components self-assemble at the nanoscale with exquisite precision-a key to their biological success in infection. Recent advances in structure determination and the development of biophysical tools such as single-molecule spectroscopy and noncovalent mass spectrometry allow unprecedented access to the detailed assembly mechanisms of simple virions. Coupling these techniques with mathematical modeling and bioinformatics has uncovered a previously unsuspected role for genomic RNA in regulating formation of viral capsids, revealing multiple, dispersed RNA sequence/structure motifs [packaging signals (PSs)] that bind cognate coat proteins cooperatively. The PS ensemble controls assembly efficiency and accounts for the packaging specificity seen in vivo. The precise modes of action of the PSs vary between viral families, but this common principle applies across many viral families, including major human pathogens. These insights open up the opportunity to block or repurpose PS function in assembly for both novel antiviral therapy and gene/drug/vaccine applications.
病毒是由核酸、蛋白质组成的实体，在某些情况下还含有脂质，它们缺乏在靶细胞外复制的能力。它们的组成部分在纳米尺度上自我组装，具有极高的精度——这是它们在感染中取得生物学成功的关键。最近在结构测定方面的进展以及单分子光谱学和非共价质谱等生物物理工具的发展，使人们能够以前所未有的方式了解简单病毒粒子的详细组装机制。将这些技术与数学建模和生物信息学相结合，揭示了基因组 RNA 在调节病毒衣壳形成过程中以前未被怀疑的作用，发现了多个分散的 RNA 序列/结构基序[包装信号（PS）]，这些基序可以协同结合同源外壳蛋白。PS 整体控制组装效率，并解释了体内观察到的包装特异性。PS 的精确作用模式在不同的病毒家族之间有所不同，但这一共同原则适用于许多病毒家族，包括主要的人类病原体。这些见解为在组装过程中阻断或重新利用 PS 功能提供了机会，既可以用于新型抗病毒疗法，也可以用于基因/药物/疫苗应用。
