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Avian flu avoids upper airway, thwarting spread in humans.

Receptor binding preferences of the H5N1 avian-influenza virus make it difficult for the infection to be transmitted between humans, two new studies show.

Using human cadaver tissues, both studies showed that H5N1 binds only to cells with a particular surface receptor molecule; in humans, these cells reside primarily in the lower respiratory tract. Cells with this receptor are located deep within human lungs, and that may inhibit spread by coughing and sneezing. This might explain why avian flu has so far been slow to spread between humans, despite nearly 200 reported human cases.

More commonly spread influenza strains tend to bind to cells with sialic acid-[alpha]-2, 6-Gal receptors, which are found throughout the respiratory system. H5N1, by contrast, prefers to bind to cells with surface receptor molecules known as sialic acid-[alpha]-2,3 Gal. In people, cells with this receptor exist deep within the lungs, which makes the avian flu virus less easily spread by coughing and sneezing.

Thijs Kuiken, Ph.D., and associates at Erasmus Medical Center in Rotterdam, (the Netherlands), exposed tissue collected from a person who had died of the bird flu to the H5N1 virus. "Attachment became progressively rarer towards the trachea," but the virus readily attached to and proliferated within the bronchioles and alveoli (Science, March 23, 2006; doi 10.1126/science.1125548; www.sciencexpress.org).

The findings, which are consistent with human pathology data, contradict the belief "that avian influenza viruses generally have little affinity for human respiratory tissues," they wrote. The virus's preference for type II pneumocytes, alveolar macrophages, and nonciliated cuboidal epithelial cells in terminal bronchioles "may contribute to the severity of the pulmonary lesion," they noted.

In the second study, Dr. Yoshihiro Kawaoka of the School of Veterinary Medicine at the University of Wisconsin, Madison, and his colleagues also found that the 2,6-Gal receptors favored by the avian virus exist only on cells deep in the human lower respiratory tract--mostly in the alveoli, with some in the bronchi.

This preference "may contribute to the inefficient human-to-human transmission of H5N1 viruses seen so far, and indicates that unimpeded transmission of the virus might require acquisition of the ability to recognize [human flu receptors]," they said.

Dr. William Schaffner, chair of the department of preventive medicine at Vanderbilt University in Nashville, Tenn., found the report by Dr. Kawaoka and his team compelling.

"This is a wonderfully elegant paper that gives a partial explanation of why the virus finds it so hard to transmit person to person," he said. "As the authors explain, if you get a big dose and inhale it deep into the lung, infection does occur and is very serious--accounting for the high fatality rate.

"The authors are careful to point out that it's going to take a series of mutations" before the virus attaches more readily to cells in the upper respiratory tract, Dr. Schaffner said. "Recombination, however, is the real concern on everyone's mind."

BY JOHN R. BELL

Associate Editor
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Author:Bell, John R.
Publication:Internal Medicine News
Geographic Code:1USA
Date:May 1, 2006
Words:495
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