Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 9190401, Israel.
Soft Matter. 2020 Mar 21;16(11):2803-2814. doi: 10.1039/c9sm02436k. Epub 2020 Feb 27.
Viruses are remarkable self-assembled nanobiomaterial-based machines, exposed to a wide range of pH values. Extreme pH values can induce dramatic structural changes, critical for the function of the virus nanoparticles, including assembly and genome uncoating. Tuning cargo-capsid interactions is essential for designing virus-based delivery systems. Here we show how pH controls the structure and activity of wild-type simian virus 40 (wtSV40) and the interplay between its cargo and capsid. Using cryo-TEM and solution X-ray scattering, we found that wtSV40 was stable between pH 5.5 and 9, and only slightly swelled with increasing pH. At pH 3, the particles aggregated, while capsid protein pentamers continued to coat the virus cargo but lost their positional correlations. Infectivity was only partly lost after the particles were returned to pH 7. At pH 10 or higher, the particles were unstable, lost their infectivity, and disassembled. Using time-resolved experiments we discovered that disassembly began by swelling of the particles, poking a hole in the capsid through which the genetic cargo escaped, followed by a slight shrinking of the capsids and complete disassembly. These findings provide insight into the fundamental intermolecular forces, essential for SV40 function, and for designing virus-based nanobiomaterials, including delivery systems and antiviral drugs.
病毒是一种卓越的自组装纳米生物材料机器，能够在广泛的 pH 值范围内暴露。极端的 pH 值会引起剧烈的结构变化，这对病毒纳米颗粒的功能至关重要，包括组装和基因组脱壳。调节货物-衣壳相互作用对于设计基于病毒的递药系统至关重要。在这里，我们展示了 pH 值如何控制野生型猿猴病毒 40（wtSV40）的结构和活性，以及其货物与衣壳之间的相互作用。使用冷冻透射电子显微镜和溶液 X 射线散射，我们发现 wtSV40 在 pH 值 5.5 至 9 之间稳定，并且仅随着 pH 值的增加而略有膨胀。在 pH 值为 3 时，颗粒聚集，而衣壳蛋白五聚体继续包裹病毒货物，但失去了它们的位置相关性。当颗粒被返回到 pH 值 7 时，感染性仅部分丧失。在 pH 值为 10 或更高时，颗粒不稳定，失去感染性并解体。使用时间分辨实验，我们发现，颗粒的膨胀首先导致解体，衣壳上戳出一个洞，遗传货物由此逃逸，随后衣壳略微收缩并完全解体。这些发现为 SV40 功能以及设计基于病毒的纳米生物材料，包括递药系统和抗病毒药物所必需的基本分子间力提供了深入的了解。
