Cell Biology of Viral Infection Lab, Instituto Gulbenkian de Ciência, Oeiras, Portugal.
European Molecular Biology Laboratory, Heidelberg, Germany.
Elife. 2023 Apr 4;12:e85182. doi: 10.7554/eLife.85182.
In biological systems, liquid and solid-like biomolecular condensates may contain the same molecules but their behaviour, including movement, elasticity, and viscosity, is different on account of distinct physicochemical properties. As such, it is known that phase transitions affect the function of biological condensates and that material properties can be tuned by several factors including temperature, concentration, and valency. It is, however, unclear if some factors are more efficient than others at regulating their behaviour. Viral infections are good systems to address this question as they form condensates as part of their replication programmes. Here, we used influenza A virus (IAV) liquid cytosolic condensates, AKA viral inclusions, to provide a proof of concept that liquid condensate hardening via changes in the valency of its components is more efficient than altering their concentration or the temperature of the cell. Liquid IAV inclusions may be hardened by targeting vRNP (viral ribonucleoprotein) interactions via the known NP (nucleoprotein) oligomerising molecule, nucleozin, both and without affecting host proteome abundance nor solubility. This study is a starting point for understanding how to pharmacologically modulate the material properties of IAV inclusions and may offer opportunities for alternative antiviral strategies.
在生物系统中，液态和固态类似的生物分子凝聚物可能包含相同的分子，但由于其独特的物理化学性质，它们的行为，包括运动、弹性和粘度，是不同的。因此，人们知道相转变会影响生物凝聚物的功能，并且材料特性可以通过多种因素（包括温度、浓度和价态）进行调节。然而，目前尚不清楚某些因素在调节其行为方面是否比其他因素更有效。病毒感染是一个很好的系统来解决这个问题，因为它们形成凝聚物作为其复制程序的一部分。在这里，我们使用甲型流感病毒 (IAV) 液态胞质凝聚物，又称病毒包涵体，提供了一个概念验证，即通过改变其成分的价态来使液态凝聚物变硬比改变其浓度或细胞温度更有效。通过靶向已知的 NP（核蛋白）寡聚分子核黄素，以及都可以在不影响宿主蛋白质组丰度和溶解度的情况下，使 vRNP（病毒核糖核蛋白）相互作用变硬，液态 IAV 包涵体可以变硬。这项研究是理解如何通过药理学调节 IAV 包涵体的物质特性的起点，并且可能为替代抗病毒策略提供机会。
