Deep defence

Why avian flu is rare in human beings

By Kirtiman Awasthi
Published: Saturday 04 July 2015

Close contact enables the viru the dreaded avian flu has affected millions of birds, but fortunately the h5n1 virus responsible does not easily infect humans. So far, the virus has infected only about 200 people worldwide. Now, two independent studies published in Nature (Vol 440, No 7083, March 23, 2006) and Science (published online, March 23, 2006) throw light on why the feared human-to-human spread of the virus has not occurred.

They suggest the answer lies in the distribution of the different receptors or binding molecules in the human respiratory tract that are preferred by avian and human flu viruses. The h5n1 virus prefers receptors common in the lower respiratory tract -- deep down in the lungs. As a result, it is not readily spread by droplet infection or cough. There has been no known case of human-to-human transmission of avian flu. In contrast, human flu virus attaches to cells in the nose and throat and so is easily transmitted from person to person.

The two studies reached similar conclusions. One of them was led by Thijs Kuiken, a virologist at Erasmus Medical Centre in the Netherlands, while the other was led by Yoshihiro Kawaoka of the University of Wisconsin-Madison in the us.

The researchers suggest that because h5n1 virus binds to receptors deep down in the respiratory tract, its transmission from birds to humans is also rare. Only in case of close contact with infected birds would the virus be able to lodge in the lower respiratory tract. In birds, the virus infects the upper respiratory tract.

The Dutch scientists used lectins -- plant molecules that bind to the same sugar complex on the cell surface that the h5n1 targets -- for their study. They used one lectin, specific to the "2,3 form" of the sugar complex common in birds, and another specific to the "2,6 form" common in humans. Testing tissues 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 that are the tiny lung sacs where oxygen/carbon dioxide exchange occurs. The same binding pattern was reported by Kawaoka's team, which also used lectins for its study. "Although site of attachment may not be the only factor in viral transmission, this information is important to better understand how h5n1 causes disease," says Jacob John at the Christian Medical College and Hospital in Vellore.

Kuiken found that the virus binding to receptors deep in the lungs could trigger an immune reaction. But the h5n1 virus can hijack the body's defence mechanism for its own growth, proving lethal. "They (set of immune reactions) explain to us why in the few cases where humans have been infected with the h5n1 virus, the main lesion is seen in the lungs, and often people that have the h5n1 virus get a severe pneumonia and can even die from it," Kuiken says. The mortality rate in infected humans is as high as 50 per cent. Kuiken says the virus can lead to a human pandemic only if it mutates to infect the upper part of the breathing passage (which would enable easy spread between humans). However, the studies do not indicate how likely such a mutation would be.

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