Influenza, or the flu, is a seasonal virus that can infect large populations and is sometimes fatal. Every season, the outbreaks are caused by different strains, which makes it hard to develop a vaccine. The evolution of influenza viruses into different strains is based on two glycoproteins on their surface: hemagglutinin (HA), which is receptor-binding, and neuroaminidase (NA), which is receptor-cleaving. It is known that they play a big role in the infection of the host cell, however, the exact mechanism is unknown.
Jurriaan Huskens and colleagues, University of Twente, Enschede, The Netherlands, have applied the concept of molecular walkers to the influenza virus. A molecular walker is a system which moves over a surface, usually controlled by Brownian motion. If the system moves in a specific direction, it needs energy, which can come from many different sources. If a walker has many legs, it is called a molecular spider.
The researchers propose that the two glycoproteins HA and NA work together to move the “spider” flu virus in a specific direction. When NA cleaves the receptors on a cell surface, HA cannot bind to them anymore, which makes the spider move away from these receptors. The cleaving frees the energy needed for this motion. This type of motion is called superdiffusive walking, i.e., the virus moves away from its starting position faster than it would by “normal” diffusion.
In order for the virus to walk efficiently over a surface, the binding and cleaving activity needs to be balanced. The faster receptors are cleaved, the faster the virus moves. However, if the cleavage is too fast, the virus dissociates from the surface. This dissociation can lead to “hop”-like motions if the virus binds at another spot of the surface, which might even help the virus to explore a large surface. With these mechanisms in place, the team proposes the influenza virus can efficiently find a place to bind to the host cell and infect it.
- Influenza as a molecular walker,
P. H. (Erik) Hamming, Nico J. Overeem, Jurriaan Huskens,
Chem. Sci. 2020.