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 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.
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.
That knowledge could help them create vaccines tailored to combat a potential pandemic. Similarly, these findings will help in the development of more effective strategies for seasonal flu, which still is a leadi
|Contact: Elizabeth Thomson|
Massachusetts Institute of Technology