Department of Physics and Astronomy, University of California, Riverside, California 92521, United States.
Songshan Lake Materials Laboratory, Dongguan, Guangdong 523808, China.
ACS Nano. 2022 Jan 25;16(1):317-327. doi: 10.1021/acsnano.1c06335. Epub 2022 Jan 12.
Simple RNA viruses self-assemble spontaneously and encapsulate their genome into a shell called the capsid. This process is mainly driven by the attractive electrostatics interaction between the positive charges on capsid proteins and the negative charges on the genome. Despite its importance and many decades of intense research, how the virus selects and packages its native RNA inside the crowded environment of a host cell cytoplasm in the presence of an abundance of nonviral RNA and other anionic polymers has remained a mystery. In this paper, we perform a series of simulations to monitor the growth of viral shells and find the mechanism by which cargo-coat protein interactions can impact the structure and stability of the viral shells. We show that coat protein subunits can assemble around a globular nucleic acid core by forming nonicosahedral cages, which have been recently observed in assembly experiments involving small pieces of RNA. We find that the resulting cages are strained and can easily be split into fragments along stress lines. This suggests that such metastable nonicosahedral intermediates could be easily reassembled into the stable native icosahedral shells if the larger wild-type genome becomes available, despite the presence of a myriad of nonviral RNAs.
简单的 RNA 病毒会自发地自我组装，并将其基因组包裹在一个称为衣壳的壳中。这个过程主要是由衣壳蛋白上的正电荷与基因组上的负电荷之间的吸引力静电相互作用驱动的。尽管它很重要，而且经过了几十年的深入研究，但在存在大量非病毒 RNA 和其他阴离子聚合物的情况下，病毒如何在宿主细胞质的拥挤环境中选择和包装其天然 RNA，仍然是一个谜。在本文中，我们进行了一系列模拟来监测病毒壳的生长，并发现了货物-衣壳蛋白相互作用如何影响病毒壳的结构和稳定性的机制。我们表明，衣壳蛋白亚基可以通过形成二十面体笼来围绕球形核酸核心组装，最近在涉及小块 RNA 的组装实验中观察到了这种二十面体笼。我们发现，所得的笼是应变的，并且可以很容易地沿着应力线分裂成片段。这表明，如果更大的野生型基因组可用，即使存在大量的非病毒 RNA，这种亚稳态二十面体中间产物也可以很容易地重新组装成稳定的天然二十面体壳。
