New molecular tool can help better understand the probability of zoonosis

The way a virus like Influenza A is transmitted from animals to humans, is still not well understood. How does the virus recognize the host cells in humans, even if the surface is different from that of animals? Researchers of the University of Twente mimicked the cell surface on a molecular scale, including the sugars to which the virus attaches. Binding is complex, not only because the number of binding places is different, but also because of the structure of the sugar molecules. The research, published in ACS Central Science, shows that a minimum number of interactions is needed for a 'successful' transfer.

Viruses bind to host cells using the well-known spike-shaped proteins at their surface. In the case of Influenza A, these proteins are hemagglutinins binding to the sugars at a cell surface, the sialic acids. The virus has to find a way to interact sufficiently strong, before it is encapsulated and does its destructive job. In essence, in human and animal cells it is the same type of binding. This is, however, not the full explanation, because many types of influenza will never be transferred to humans. A crucial difference is he number of sialic acids on a surface. The structure and length of the sugar molecules in humans is also different, resulting in less opportunities for binding. An avian virus does not have a good starting point when it 'lands' on a human cell surface: it doesn't 'see' all the necessary bindings. Still, it has to find a minimum of around eight interactions to be effective, the research shows.

Estimating risk of zoonosis

In order to determine the binding strength, the researchers have mimicked the cell surface with sialic acids on it. They created a gradient, ranging from a low density of molecules to a higher density. At low densities, a virus doesn't have sufficient interaction opportunities. The length and type of the molecules are decisive as well. The new tool gives valuable insight in the binding opportunities, and the infection risk. Although this research focused on Influenza A, the new insights improve our understanding of other viruses, like corona viruses, as well. So, the tool can be help us understand the probability of zoonosis.

Multidisciplinary team

The research has been done in the Molecular Nanofabrication of Prof Jurriaan Huskens. This group is part of UT's MESA+ Institute. A multidisciplinary team was formed including virologists (Royal GD veterinary lab), sugar and biology chemists (Utrecht University), and experts of molecular dynamics (University of Georgia) and theoretical/computational physics (TU Eindhoven).