Greg Laden's Blog

A quick word about viruses and receptor sites. I have always found the terminology to be a bit counter-intuitive and possibly misleading. The word "receptor site" almost sounds like a feature that a cell has in order to receive, allow in, provide a reception for a virus, as though the cell somehow "wanted" the virus to come on in and make itself comfortable. Of course, nothing could be farther from the truth. Receptor cites are features of a cell surface (the outside of the cell membrane) that are there for some reason that has to do with cell function. The receptor site has some day to day function. The virus is exploiting the molecular characteristics of this feature to gain (unwanted) entry to the cell. There is no viral welcome mat!

Anyway, to continue with the press release:

The researchers found that a virus's ability to infect humans depends on whether it can bind to one specific shape of receptor on the surface of human respiratory cells.

"Now that we know what to look for, this could help us not only monitor the bird flu virus, but it can aid in the development of potentially improved therapeutic interventions for both avian and seasonal flu," said Ram Sasisekharan, MIT Underwood Prescott Professor of Biological Engineering and Health Sciences and Technology, and the senior author of a paper on the work that appears in the Jan. 6 issue of Nature Biotechnology.

Flu viruses come in many strains, and not all of them can infect humans. Strains known as H1 or H3 have "jumped" from birds to humans and hence are tailored to attack cells of the human upper respiratory tract. H5 strains are usually confined to birds, but when they do infect humans they can have very high fatality rates.

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Scientists already knew that whether an influenza virus infects humans depends on whether its hemagglutinin, a protein found on the virus surface, can bind to sugar (or glycan) receptors in the respiratory tract. Human respiratory cells have glycan receptors classified as alpha 2-6; avian respiratory cells' glycan receptors are known as alpha 2-3. This classification is based on how the sugars are linked together when they are displayed on cells.

Until now, scientists had believed that a genetic switch that allows the virus to bind to alpha 2-6 receptors instead of alpha 2-3 receptors is responsible for avian viruses' ability to jump to humans.

The MIT study shows that that view does not adequately explain how viruses evolve to infect humans. ... it is the ability of a flu virus to bind to a certain shape, or topology, of specific alpha 2-6 glycan receptor that determines whether it will infect humans.

Alpha 2-6 glycan receptors come in two shapes--one that resembles an umbrella, and another that resembles a cone. The MIT team found that to infect humans, flu viruses must bind to the umbrella-shaped alpha 2-6 receptor.

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This new interpretation explains inconsistencies that plagued the previous model, according to Sasisekharan. For example, some flu strains that can bind to alpha 2-6 receptors do not infect humans very well. It turns out that those viruses bind to cone-shaped alpha 2-6 receptors, which are present in the human respiratory tract but in much smaller numbers than umbrella-shaped alpha 2-6 receptors.

This new paradigm should help researchers develop a better way to track the evolution of avian flu leading to human adaptation, Sasisekharan said. Now, they know to look for avian viruses that have evolved the ability to bind to umbrella-shaped alpha 2-6 receptors.

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