MIT Study Identifies Key Receptor in Bird-to-Human Flu Transmission

MIT researchers have uncovered a critical difference between flu viruses that infect birds and humans which has to do with whether a virus can bind to one specific shape of receptor on the surface of human respiratory cells.

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, 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.

"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 appeared in the Jan. 6 issue of Nature Biotechnology.

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 leading cause of death.

For more information, visit www.nature.com/index.html.

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