Understanding how viruses survive in different settings could lead to new ways to fight them. Researchers have now built a complete model of the outer envelope of a flu virus particle for the first time, allowing them to simulate how the membrane behaves under various conditions.
The influenza A virion seems to infect seasonally and has a wide range of survival times in different environments. To better understand its infectivity at the molecular level, Oxford’s Tyler Reddy and colleagues focused on the role of lipids in the virus particle’s membrane, which remains poorly understood.
To start, the team rendered the virus particle as a large ball of loosely-packed lipids with viral spike proteins embedded in the lipid membrane (see image above). These glycoprotein protrusions on the surface play a key role in the strength of the interactions between virus particles and host cells—which are determined by the number of spike proteins that can engage with receptors. (That’s what differentiates influenza A subtypes, which includes H1N1 “swine flu” and H5N1 “bird flu.”) The 73-nanometer ball contracts down to 59 nanometers in just 300 nanoseconds, which is about one-fifteenth of the simulation’s run-time.
Then, the team was able to generate various trajectories using a range of temperatures and various lipid compositions. Their simulation revealed that those viral spike proteins spread out, rather than aggregate together. "If the separation of the spike proteins is compatible with the 'arms' of Y-shaped, bivalent antibodies, this information might be exploited in therapeutic design, so that two antigens may be bound simultaneously for enhanced association," Reddy explains in a news release.
This approach for studying the membrane envelope's structure and dynamics could also be used to understand the virus particle’s survival in different environments. For example, previous research has suggested that the presence of influenza A in freshwater rivers allowed waterfowl to be exposed both to the flu source as well as to residual anti-viral substances from human population runoff—which might lead to drug-resistant flu strains. But for now, Reddy’s simulation can only monitor the virus particle’s stability on the micro-second scale, and the new challenge will be figuring out a way to study stability over much longer time scales.
The work was presented at the annual Biophysical Society meeting in Baltimore this week.