Sasisekharan noted that recent studies have shown that the hemagglutinin protein from bird flu viruses has on occasion attached to glycans of the upper airways. The surprising finding, he explained, is that the virus didnt always spread effectively.
This was a conundrum, said Sasisekharan.
To solve it, he and his team turned to the Consortium for Functional Glycomics (CFG), an initiative supported by NIGMS to explore the interactions between proteins and different types of sugars.
Mining data from the CFG glycan array, a tool for quickly screening protein-glycan binding preferences, Sasisekharan began to explore the structures of the different sugar chains coating upper respiratory tract cells.
We found remarkable diversity, he said. Even though these glycans are all linked the same way chemically, they have very different shapes.
According to the results, glycans of upper respiratory tract cells come in two main varieties: short and cone-shaped, and long and umbrella-shaped.
When the researchers combined this information with data from experiments and the glycan array, they found that the hemagglutinin protein from human-adapted flu viruses attached specifically to the long glycans of the upper respiratory tract. They also confirmed that the hemagglutinin from H5N1 viruses bound mainly to the cone-shaped glycans found in the lower respiratory tract.
These findings suggest that for the H5N1 bird flu virus to infect people and sustain its spread in humans, it must adapt so that it can latch onto the umbrella-shaped glycans of the upper respiratory tract.
Until now, we had an incomplete understanding of avian flu hemagglutinin and how the protein must adapt to humans, said Sasisekharan.
The new knowledge may unlock strategies for tracking mutations in the avian flu virus that allow it to bind to l
|Contact: Alisa Machalek|
NIH/National Institute of General Medical Sciences