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April 03, 2006

Bird flu's human-attack pathway revealed

Two separate research groups have independently discovered why the H5N1 bird flu virus causes lethal pneumonia in people, but is – so far – hard for people to catch. In the process, they have found a way to predict which mutations might make the virus more contagious, and potentially become a pandemic strain. To date, confirmed human deaths from the disease stand at 103 worldwide

The H5N1 virus binds to sugars on the surface of cells deep in human lungs, but not to cells lining the human nose and throat. So report the two research teams, led by Thijs Kuiken at Erasmus University in Rotterdam, and Yoshihiro Kawaoka at the Universities of Tokyo, Japan and Wisconsin at Madison, US.

This fits the few autopsies that have been performed on H5N1 victims, who had damage to the alveoli – the delicate sacs deep in the lungs, where oxygen enters the blood.

Flu normally travels between people by being sneezed out and breathed in through the nose and throat. Both groups concluded that poor binding of the H5N1 high in the respiratory tract might be why the virus has so far not been able to spread easily between people – a major factor keeping it from becoming pandemic.

Deep inside

The Wisconsin team used lectins – plant molecules that bind to the same complex sugars on the cell surface where the flu virus attaches to cells – to identify how different versions of the sugar molecule vary in humans. They used one lectin specific to the "2,3 form" of the sugar common in birds – which H5N1 is known to prefer, and another specific to the "2,6 form" more common in people.

Testing tissue slices from the human respiratory tract, they found that 2,6 receptors were common in the nose and throat, but 2,3 receptors – H5N1’s preferred site – were common in the alveoli.

The Dutch group used the killed H5N1 virus itself, and saw the same pattern as the Wisconsin team, with binding in the deep lungs but not the nose and throat.

Repair hijack

Both groups found these receptors, or viral binding, especially in cells called type 2 alveolar cells. These actively dividing cells repair and maintain the tiny lung sacs, so H5N1’s binding of these particular cells might explain why H5N1 pneumonia is so severe. The virus can also hijack the machinery it needs to replicate more easily in these active cells than in neighbouring, non-dividing cells.

The Dutch team also found binding to alveolar macrophages – white blood cells which can trigger the inflammatory immune reaction, which often kills in pneumonia cases.

Their technique might allow scientists to predict what H5N1 could do next. “We will now try to look at what mutations in the virus improve binding in the upper respiratory tract,” Kuiken told New Scientist. That could show what mutations to watch for as H5N1 continues to spread around the globe.

They will also study which other human tissues H5N1 can bind to. Cases so far suggest it might affect the gut and most worryingly, the brain.

Posted by dymaxion at April 3, 2006 08:53 PM

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