Zeng Cheng, Scott Liam, Malyutin Andrey, Zandi Roya, Van der Schoot Paul, Dragnea Bogdan
Department of Chemistry, Indiana University, Bloomington, Bloomington, Indiana 47405, United States.
Department of Physics and Astronomy, University of California at Riverside, Riverside, California 92521, United States.
J Phys Chem B. 2021 Feb 25;125(7):1790-1798. doi: 10.1021/acs.jpcb.0c10947. Epub 2021 Feb 12.
Viruses avoid exposure of the viral genome to harmful agents with the help of a protective protein shell known as the capsid. A secondary effect of this protective barrier is that macromolecules that may be in high concentration on the outside cannot freely diffuse across it. Therefore, inside the cell and possibly even outside, the intact virus is generally under a state of osmotic stress. Viruses deal with this type of stress in various ways. In some cases, they might harness it for infection. However, the magnitude and influence of osmotic stress on virus physical properties remains virtually unexplored for single-stranded RNA viruses-the most abundant class of viruses. Here, we report on how a model system for the positive-sense RNA icosahedral viruses, brome mosaic virus (BMV), responds to osmotic pressure. Specifically, we study the mechanical properties and structural stability of BMV under controlled molecular crowding conditions. We show that BMV is mechanically reinforced under a small external osmotic pressure but starts to yield after a threshold pressure is reached. We explain this mechanochemical behavior as an effect of the molecular crowding on the entropy of the "breathing" fluctuation modes of the virus shell. The experimental results are consistent with the viral RNA imposing a small negative internal osmotic pressure that prestresses the capsid. Our findings add a new line of inquiry to be considered when addressing the mechanisms of viral disassembly inside the crowded environment of the cell.
病毒借助一种称为衣壳的保护性蛋白质外壳，避免病毒基因组暴露于有害因子。这种保护屏障的一个附带作用是，细胞外部可能高浓度存在的大分子无法自由扩散穿过它。因此，在细胞内部甚至可能在细胞外部，完整的病毒通常处于渗透压应激状态。病毒以多种方式应对这种类型的应激。在某些情况下，它们可能利用这种应激进行感染。然而，对于单链RNA病毒（最为丰富的病毒类别），渗透压应激对病毒物理性质的影响程度和影响方式实际上仍未得到探索。在此，我们报告了正链RNA二十面体病毒的一个模型系统——雀麦花叶病毒（BMV）如何响应渗透压。具体而言，我们研究了在受控的分子拥挤条件下BMV的力学性质和结构稳定性。我们表明，BMV在较小的外部渗透压下会得到力学增强，但在达到阈值压力后开始屈服。我们将这种机械化学行为解释为分子拥挤对病毒外壳“呼吸”波动模式熵的影响。实验结果与病毒RNA施加一个小的负内部渗透压从而对衣壳施加预应力相一致。我们的发现为探讨细胞拥挤环境中病毒解体机制时需要考虑的问题增添了新的研究方向。
