Sugar on cell surface identified as key factor in flu infection
January 7th, 2008 - 5:30 pm ICT by adminLondon, Jan 7 (ANI): Scientists at the Massachusetts Institute of Technology in Cambridge have found that sugar on cell surfaces is a key factor that is necessary for sustaining the spread of flu between people.
The study, they say is important as it offers new insights into how the H5N1 avian flu virus or bird flu would have to change in order to infect humans on a large scale.
The only way the virus will be able to infect cells of the human upper respiratory tract is by gaining access through a separation of the sugar molecules coating the cells of the upper airways.
The finding, the researchers led by Ram Sasisekharan, Ph.D. state, could provide a means for holding back the spread between people.
The birdflu virus has infected hundreds of people, however the passing on of the virus from one person to another has been limited.
In order for a human epidemic to occur, experts have agreed that the bird flu virus must infect the cells lining our noses and throats. The virus would then be spread to others through coughing or sneezing.
“Using an approach that combines experimentation and database analysis, Sasisekharan’s team has changed our view of flu viruses and how they must adapt to infect us,” Nature Biotechnology quoted Dr. Jeremy M. Berg, director of the National Institute of General Medical Sciences, the NIH component that supported the research, as saying.
“The work may improve our ability to monitor the evolution of the H5N1 virus and thwart potential outbreaks,” he added.
Our bodies have chains of sugars called glycans, which sit on the surface of our cells and control the gates through which different molecules enter. In order for a virus to gain access to a cell, proteins on the virus’s surface must bind to certain glycans.
Hemagglutinin is the binding protein for flu viruses, however each protein can be different with each flu strain and, as a result, latch on to glycans from different types of cells.
It was found that the protein from human-adapted flu viruses favoured the sugars dotting the cells of the nose and throat, the one from bird flu viruses opted for glycans on cells deeper in the respiratory tract.
In the recent studies conducted by Sasisekharan, he noted that the hemagglutinin protein from bird flu viruses has on occasion attached to glycans of the upper airways. What he found surprising about the find was that the virus didn’t always spread effectively.
To get to the bottom of the mystery, 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.”
They found that glycans of the upper respiratory tract cells came in two main varieties, short and cone-shaped, and long and umbrella-shaped.
The researchers combined this information with data from experiments and the glycan array, and 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.
The findings suggested that for the H5N1 bird flu virus to infect people and sustain its spread in humans, it requires to 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 findings may develop ways for tracking mutations in the avian flu virus that allow it to bind to long glycans, point to new therapeutic targets for both seasonal and pandemic flu, and expand our basic knowledge of glycans and their diversity. (ANI)
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