Virus Assembly Pathways Inside a Host Cell
Virus Assembly Pathways Inside a Host Cell
复制标题
DOI：
10.1021/acsnano.1c06335
复制
发表时间：
2022-01-12
期刊：
影响因子：
17.1
通讯作者：
Zandi, Roya
中科院分区：
文献类型：
--
作者：
Panahandeh, Sanaz;Li, Siyu;Zandi, Roya
简单的RNA病毒自发地自我组装，并将它们的基因组封装到一个称为衣壳的壳中。这一过程主要是由衣壳蛋白上的正电荷和基因组上的负电荷之间吸引的静电相互作用所驱动的。尽管它很重要，而且经过了几十年的密集研究，但病毒如何在宿主细胞细胞质的拥挤环境中，在大量非病毒RNA和其他阴离子聚合物存在的情况下选择和包装其天然RNA仍然是一个谜。在本文中，我们进行了一系列的模拟来监测病毒外壳的生长，并找到了衣壳蛋白相互作用影响病毒外壳结构和稳定性的机制。我们发现，外壳蛋白亚基可以通过形成非二十面体笼子来组装在球形核酸核心周围，这是最近在涉及小片段RNA的组装实验中观察到的。我们发现，得到的笼子是应变的，很容易沿着应力线分裂成碎片。这表明，尽管存在大量的非病毒RNA，但如果获得更大的野生型基因组，这种亚稳定的非二十面体中间体很容易重组到稳定的天然二十面体外壳中。
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.