How Avian Flu May Become Human

Scientists at MIT have identified a characteristic within the influenza virus that makes it dangerous for some species and not others.

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. The new work reveals that, more specifically, 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.
Thus, Sasisekharan [Ram Sasisekharan, MIT Underwood Prescott Professor of Biological Engineering and Health Sciences and Technology] and his team have redefined the host receptor for influenza and the criteria for how H5N1 can jump to humans. They did so by showing that the shape of the sugars–and not the type of linkage–is the key determinant for human adaptation of these deadly viruses.

Press release: MIT finds key to avian flu in humans
Abstract in Nature Biotechnology…