UMR Biologie du Fruit et Pathologie, INRA, Université de Bordeaux, Villenave d'Ornon, France.
CNRS 5320, INSERM U1212, Pessac, France.
Mol Biol Evol. 2018 Jan 1;35(1):38-49. doi: 10.1093/molbev/msx249.
Intrinsic disorder (ID) in proteins is defined as a lack of stable structure in physiological conditions. Intrinsically disordered regions (IDRs) are highly abundant in some RNA virus proteomes. Low topological constraints exerted on IDRs are expected to buffer the effect of numerous deleterious mutations and could be related to the remarkable adaptive potential of RNA viruses to overcome resistance of their host. To experimentally test this hypothesis in a natural pathosystem, a set of four variants of Potato virus Y (PVY; Potyvirus genus) containing various ID degrees in the Viral genome-linked (VPg) protein, a key determinant of potyvirus adaptation, was designed. To estimate the ID contribution to the VPg-based PVY adaptation, the adaptive ability of the four PVY variants was monitored in the pepper host (Capsicum annuum) carrying a recessive resistance gene. Intriguingly, the two mutants with the highest ID content displayed a significantly higher ability to restore infection in the resistant host, whereas the less intrinsically disordered mutant was unable to restore infection. The role of ID on virus adaptation may be due either to a larger exploration of evolutionary pathways or the minimization of fitness penalty caused by resistance-breaking mutations. This pioneering study strongly suggests the positive impact of ID in an RNA virus adaptive capacity.
蛋白质中的固有无序（ID）被定义为在生理条件下缺乏稳定结构。固有无序区域（IDR）在一些 RNA 病毒的蛋白质组中高度丰富。对 IDR 施加的低拓扑约束预计将缓冲大量有害突变的影响，并且可能与 RNA 病毒克服宿主抗性的显著适应潜力有关。为了在自然病理系统中实验验证这一假设，设计了一组含有不同 ID 程度的马铃薯 Y 病毒（PVY；马铃薯病毒属）的四个变体，其中包含病毒基因组连接（VPg）蛋白中的关键决定因素，即影响病毒适应性的决定因素。为了估计 ID 对基于 VPg 的 PVY 适应性的贡献，在携带隐性抗性基因的辣椒（Capsicum annuum）宿主中监测了四个 PVY 变体的适应性能力。有趣的是，两个具有最高 ID 含量的突变体在抗性宿主中恢复感染的能力显著提高，而 ID 含量较低的突变体则无法恢复感染。ID 对病毒适应性的作用可能是由于更大程度地探索进化途径，或者是由于降低了抗性突变引起的适应性代价。这项开创性的研究强烈表明 ID 在 RNA 病毒适应能力中的积极影响。
