论文标题
扩散介导的发芽的力学及其对病毒复制和感染的影响
Mechanics of diffusion-mediated budding and implications for virus replication and infection
论文作者
论文摘要
芽允许细胞中的病毒复制和大分子分泌。它涉及芽的形成，即从细胞膜中的产物，将其演变成一个信封。芽形成的最大能量障碍是膜的挠度，主要归功于核素 - 膜膜粘附。跨膜蛋白（TPS）后来形成病毒配体，是粘附的主要启动子，由于诱导的自发曲率，可以容纳膜弯曲。粘合剂TPS必须从偏远区域跨膜扩散才能聚集在芽表面上，因此扩散性控制动力学。本文提出了一个简单的模型，以描述扩散介导的萌芽，从而揭示了重要的尺寸限制和尺寸依赖性动力学。预测的最佳病毒率半径（给出最快的萌芽）是针对冠状病毒，HIV，流感和肝炎的实验的。假设病毒体和遗传大小的指数复制，该模型可以预测病毒群体的大小分布。这是针对SARS-COV-2实验的验证。以上所有比较都取决于萌芽所带来最紧密的约束的前提。正如本文所证明的那样，在大多数情况下，在大多数情况下，提出的模型被扩展以描述通过受体和网格蛋白介导的内吞作用以及通过膜融合来描述病毒感染。
Budding allows virus replication and macromolecular secretion in cells. It involves the formation of a bud, i.e. an outgrowth from the cell membrane that evolves into an envelope. The largest energetic barrier to bud formation is membrane deflection and is trespassed primarily thanks to nucleocapsid-membrane adhesion. Transmembrane proteins (TPs), which later form the virus ligands, are the main promotors of adhesion and can accommodate membrane bending thanks to an induced spontaneous curvature. Adhesive TPs must diffuse across the membrane from remote regions to gather on the bud surface, thus, diffusivity controls the kinetics. This paper proposes a simple model to describe diffusion-mediated budding unraveling important size limitations and size-dependent kinetics. The predicted optimal virion radius, giving the fastest budding, is validated against experiments for Coronavirus, HIV, Flu, and Hepatitis. Assuming exponential replication of virions and hereditary size, the model can predict the size distribution of a virus population. This is verified against experiments for SARS-CoV-2. All the above comparisons rely on the premise that budding poses the tightest size constraint. This is true in most cases, as demonstrated in this paper, where the proposed model is extended to describe virus infection via receptor- and clathrin-mediated endocytosis, and via membrane fusion.
