Kinetics and Optimality of Influenza A Virus Locomotion

Area of Science:

• Virology
• Biophysics
• Computational Biology

Background:

• Influenza A viruses (IAVs) infect airway cells by traversing extracellular mucus.
• Mucus contains sialic acid, which binds to viral ligands and can be modified by viral enzymes.
• Filamentous IAVs exhibit directed motion along mucus surfaces.

Purpose of the Study:

• To elucidate the mechanism of directed persistent motion in filamentous IAVs on sialic acid-coated surfaces.
• To investigate the role of system equilibrium features and ligand distribution in viral transport dynamics.
• To explore the implications of viral transport efficiency for infection and evolution.

Main Methods:

• Stochastic simulations were employed to model viral motion.
• Mean-field theory was utilized to analyze the underlying dynamics.
• Analysis focused on the interplay between viral ligands, mucus properties, and enzyme kinetics.

Main Results:

• IAVs utilize a "burnt-bridge" Brownian ratchet mechanism for directed translational motion.
• System equilibrium features significantly influence out-of-equilibrium dynamics.
• Asymmetric ligand distribution enhances directed transport, with viruses operating in an optimal parameter range.
• Enzyme kinetics may be evolutionarily adapted for efficient mucus transport.

Conclusions:

• The "burnt-bridge" Brownian ratchet provides a mechanism for IAVs to navigate mucus.
• Optimal viral parameterization suggests evolutionary adaptation for efficient host cell entry.
• Findings offer insights into viral pathogenesis, zoonotic transmission, and potential therapeutic targets.