Mechanics of diffusion-mediated budding and implications for virus replication and infection

TL;DR

This paper presents a model of diffusion-mediated viral budding that predicts optimal virus size and kinetics, validated with experimental data for various viruses, and extends to infection mechanisms like endocytosis and membrane fusion.

Contribution

It introduces a simple, size-dependent model for virus budding kinetics and size distribution, validated with experimental data, and extends to infection processes.

Findings

Optimal virion radius for fastest budding identified

Model validated with experimental data for multiple viruses

Size constraints are critical in virus budding and infection

Abstract

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.