A scientific article titled ‘Hierarchical multivalent effects control influenza host specificity’ was published today in the professional journal ACS Central Science of the American Chemical Society. The research, a cooperative project between researchers at Royal GD (Erhard van der Vries) and the University of Twente (Jurriaan Huskens), describes the development of a biosensor to document the binding of influenza viruses to host cells at the molecular level.
There is still no certainty about how a virus such as Influenza A is transmitted from animals to humans. How does the virus recognise ‘host cells’ in humans, even though their surface may differ from that in animals? Researchers at the University of Twente have mimicked the cell surface architecture with glycans to which a virus attaches, at the molecular level. The binding process is complex, because the length of the molecules varies between humans and animals. It is clear that a minimum value is needed for the number of binding receptors, for transmission to be ‘successful’. The research has been published in ACS Central Science.
Multidisciplinary research focuses on Influenza A, but also provides insight into the transmission and binding of other types of viruses. Viruses attach themselves via the ‘spikes’ on their surface, to a host cell. In the case of influenza, these spikes are haemagglutinin proteins that bind to glycans on the cell surface, the sialic acids. The viruses ensure that they bind stably enough before becoming encapsulated and doing their destructive work. Although this binding process is comparable in animals and humans, it is not a simple explanation for transmission, as there are many types of influenza that never transfer to humans. The density of sialic acids on a surface varies, and along with it the chance of successful binding. The type and length of the molecules also varies, giving the virus fewer opportunities for multiple interactions with a single molecule. The new research suggests that an avian influenza virus does not find the most favourable breeding ground on a human cell surface: it does not ‘recognise’ all opportunities for interaction. At the same time, the research shows that a minimum number is required: the threshold is approximately eight interactions.
Binding of a virus to the molecules on the surface. All the figures show low density on the left and high density on the right. In (i) and (ii), the virus also binds at low receptor density, thanks to the length of the molecules. In (iii), it may still bind at high density, while in (iv) neither the structure nor length is favourable, and the virus will not bind at all.
To determine the binding strength of the virus, the researchers mimicked a cell surface with sialic acids, applying a gradient: from few to multiple molecules per surface unit. At too low a density of the glycans, the virus has no opportunity to sufficiently attach itself. This is reinforced by variation in type and length. The newly developed tool gives instant insight into the binding and thereby the risk of infection by a virus. Although focused on Influenza A in this case, the insights are also important for other viruses such as coronaviruses. The tool can be used to learn to estimate the risk of a virus causing a zoonosis.
This research was conducted in the Molecular Nanofabrication (MESA+ Institute) group of Professor Jurriaan Huskens, together with a multidisciplinary team comprising virologists (Royal GD), glycologists and biochemists (University of Utrecht), and experts in molecular dynamics (University of Georgia, US) and theoretical/computational physicists (Eindhoven University of Technology).
The paper titled ‘Hierarchical multivalent effects control influenza host specificity’, by Nico Overeem, Erik Hamming, Oliver Grant, Daniele Di Iorio, Malte Tieke, Candelaria Bertolini, Zeshi Li, Gaël Vos, Robert de Vries, Robert Woods, Nicholas Tito, Geert-Jan Boons, Erhard van der Vries and Jurriaan Huskens was published today in ACS Central Science of the American Chemical Society.
Read the paper