Mechanical Engineering Department, School of Biomedical Engineering, Institute of Applied Mathematics, University of British Columbia, Vancouver, BC Canada V6T1Z4.
J R Soc Interface. 2022 Nov;19(196):20220525. doi: 10.1098/rsif.2022.0525. Epub 2022 Nov 2.
Budding allows virus replication and macromolecular secretion in cells through the formation of a membrane protrusion (bud) 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 unravelling 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.
芽殖通过形成一个膜突起（芽）来允许病毒在细胞中复制和大分子分泌，该突起演变成包膜。芽殖形成的最大能量障碍是膜的弯曲，主要得益于核衣壳-膜的粘附。随后形成病毒配体的跨膜蛋白（TP）是粘附的主要促进剂，并且由于诱导的自发曲率，可以容纳膜弯曲。粘附性的 TPs 必须从远程区域扩散穿过膜，聚集在芽的表面，因此，扩散性控制着动力学。本文提出了一个简单的模型来描述扩散介导的芽殖，揭示了重要的尺寸限制和尺寸相关的动力学。预测的最佳病毒半径，给出最快的芽殖，针对冠状病毒、HIV、流感和肝炎的实验进行了验证。假设病毒粒子的指数复制和遗传大小，该模型可以预测病毒群体的大小分布。针对 SARS-CoV-2 的实验进行了验证。所有上述比较都基于芽殖构成最严格的尺寸约束的前提。在大多数情况下都是如此，正如本文所证明的那样，所提出的模型扩展到描述通过受体和网格蛋白介导的胞吞作用以及通过膜融合进行的病毒感染。
