Scientists Find Key to What Could Make Bird Flu a Human Pandemic
By Brandon Keim 01.06.08 | 1:00 PM
Scientists have identified a key mechanism necessary for bird flu to morph from a rare but deadly infection into a pandemic that could kill millions of people.
MIT scientists reported in Sunday's issue of Nature Biotechnology that the shape of certain structures in the virus could be key to allowing it to easily pass from human to human. In birds, the shape of the structures match the shape of sugars in the animals' respiratory tracts, allowing the infection to easily latch onto the animals. In humans, those shapes don't match up -- but if the virus morphed so they did, it could lead to a pandemic.
"We’re like a sitting duck, waiting for an H5N1 virus that can attach to us," said Richard Cummings, an Emory University biochemist and influenza cell specialist who did not participate in the study. "This research moves us to the point where we can start anticipating what might happen."
Since its 1997 outbreak in Hong Kong, H5N1 avian influenza has spread rapidly around the world -- first in poultry, then in wild birds. It’s killed millions of fowl in 66 countries, most since 2003. But it has yet to become a common human killer. What H5N1 lacks in human infectiousness, however, it makes up for in lethality: of 348 people in 14 countries infected by H5N1 since 2003, 216 died.
The virus is constantly evolving. Each infected bird population is a giant petri dish of potential mutations. If H5N1 learns to spread among people as well as it spreads in birds, the consequences could be catastrophic. A 1918 influenza pandemic killed 50 million people, and outbreaks in 1957 and 1968 killed another three million.
With H5N1, humans have so far benefited from the differences between cells in our noses and throats and those of birds -- but that could change. With the MIT scientists' discovery, doctors can monitor H5N1 strains for early evidence of human virulence. They may also make precisely targeted vaccines and drugs in advance of outbreaks.
Massachusetts Institute of Technology cell biologist and study co-author Ram Sasisekharan and his colleagues studied two strains of avian influenza, H3N2 and H1N1 -- the latter closely related to the killer 1918 virus -- that spread from birds to people. They found that the viruses connected to particular types of sugar found on the surface of upper respiratory tract cells.
These sugars act like doorknobs. When a single viral particle meets a cell, it grapples with the sugar molecule, using it as entry point for invasion. Once inside the cell, the virus produces copies of itself that soon explode outwards, infecting new cells and becoming airborne with each breath.
Both H3N2 and H1N1 latched onto sugar configurations known as a2-6 sialylated glycans, found exclusively in our upper respiratory tracts. Birds possess slightly different sugars, known as a2-3 sialylated glycans, to which H5N1 connects easily. In order to spread efficiently between people, said Sasisekharan, H5N1 would have to configure itself to our own sugars.
Sasisekharan’s team then identified the unique shapes taken by our a2-6 sialylated glycans, which vary between regions of the respiratory tract. They identified two shapes, roughly resembling an umbrella and a cone, that would be the likely connecting points for a pandemic H5N1 strain.
"People hadn't really thought about the shape of the structures as being so relevant in this regard," Cummings said.
Scientists can now search for evidence of necessary configurations in new strains of H5N1, perhaps stifling them before the transformation is complete. They can also predict the genetic mutations necessary for H5N1 to bind to our sugars, and use the knowledge to develop specifically targeted vaccines and drugs.
"Rather than looking for a needle in a haystack, this lets us focus," Sasisekharan said.
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