Kinetics and optimality of influenza A virus locomotion

Abstract

Influenza A viruses (IAVs) must navigate through a dense extracellular mucus to infect airway epithelial cells. The mucous layer, composed of glycosylated biopolymers (mucins), presents sialic acid that binds to ligands on the viral envelope and can be irreversibly cleaved by viral enzymes. It was recently discovered that filamentous IAVs exhibit directed persistent motion along their long axis on sialic acid-coated surfaces. This study demonstrates through stochastic simulations and mean-field theory, how IAVs harness a ‘burnt-bridge’ Brownian ratchet mechanism for directed persistent translational motion. Importantly, our analysis reveals that equilibrium features of the system primarily control the dynamics, even out-of-equilibrium, and that ligand asymmetry allows for more robust directed transport. We show viruses occupy the optimal parameter range (‘Goldilocks zone’) for efficient mucous transport, possibly due to the evolutionary adaptation of enzyme kinetics. Our findings suggest novel therapeutic targets and provide insight into possible mechanisms of zoonotic transmission.