Unraveling Influenza A Virus Motion: Insights for Antiviral Strategies
December 13, 2024A collaborative team of bioengineers from UC Berkeley’s Biohub and the Chan Zuckerberg Initiative has developed a simulation to model the movement of the influenza A virus (IAV) through host tissue. This breakthrough, detailed in Physical Review Letters, could pave the way for innovative methods to halt viral spread.
Table of Contents
A Unique Mechanism of Viral Motion
Unlike most biological motion powered by molecular motors fueled by chemical energy, IAV employs an unconventional method. Upon entering the host’s airways, the virus binds to the mucous fibers lining the respiratory tract, utilizing the hemagglutinin (HA) protein on its surface to attach to receptor molecules. Simultaneously, the neuraminidase (NA) protein cleaves these receptors, preventing backtracking and enabling forward propulsion—an approach termed the “burnt-bridge mechanism.”
Burrowing through. The influenza A virus propels itself through a mucous layer. The asymmetrical arrangement of receptor-binding proteins (hemagglutinin, blue) and receptor-cleaving proteins (neuraminidase, red) drives forward motion through these proteins’ interactions with receptor molecules on the surfaces of mucous fibers.
Simulating the Virus’s Motion
The research team built a model to simulate this unique propulsion system, representing receptor bonds as spring-like forces acting on the virus. Their findings revealed that efficient viral movement requires a delicate balance: binding must be strong enough to enable traction but weak enough to allow timely release. The simulation further demonstrated that clustering HA and NA proteins at opposite ends of the virus significantly enhances movement efficiency, stabilizing the burnt-bridge mechanism across a broader range of conditions.
Implications for Antiviral Therapies
The study provides critical insights into potential antiviral strategies. The researchers propose targeting HA’s binding strength, as their model indicates IAV locomotion is highly sensitive to this parameter but less affected by NA’s receptor-cleaving activity. Drugs designed to disrupt HA’s optimal binding range could effectively hinder the virus’s ability to spread within the host.
A) A virion (not to scale) navigates the complex heterogeneous and flowing mucous layer (1–10 µm) composed of highly glycosylated, entangled mucin fibers. (B) Coarse-grained model of a virion as a rigid elongated shell, positioned at a constant offset above a 1D substrate consisting of uniformly coated glycoproteins decorated with SA receptors. Credit: https://www.biorxiv.org/content/10.1101/2024.05.06.592729v2
Broader Applications and Insights
Beyond therapeutic implications, this research sheds light on how viral strains adapt to specific host environments by evolving optimal binding and cleaving properties. Such knowledge could aid in predicting cross-species transmission risks and managing potential outbreaks.
“This work highlights the complex interplay of physical principles and biological mechanisms,” noted Nancy Forde, a biophysicist at Simon Fraser University, adding that the findings align closely with observed human IAV behavior.
The study underscores the potential of physics-based modeling in unraveling the mysteries of viral motion and advancing antiviral drug development.
More information: Siddhansh Agarwal et al, Kinetics and Optimality of Influenza A Virus Locomotion, Physical Review Letters (2024). DOI: 10.1103/PhysRevLett.133.248402. On bioRxiv: www.biorxiv.org/content/10.110 … /2024.05.06.592729v2
