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Minor Mutations Found in Bird Flu Virus

Changes Increase Chances of Human Infection

March 20, 2006

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Scientists at The Scripps Research Institute, the Centers for Disease Control, and the Armed Forces Institute of Pathology have identified what the researchers described as a possible pathway for a particularly virulent strain of the avian flu virus to "gain a foothold in the human population."

The H5N1 avian influenza virus, commonly known as "bird flu," is a highly contagious and deadly disease in poultry. So far, its spread to humans has been limited, with 177 documented severe infections, and nearly 100 deaths in Indonesia, Vietnam, Thailand, Cambodia, China, Iraq, and Turkey as of March 14, 2006, according to the World Health Organization.

"With continued outbreaks of the H5N1 virus in poultry and wild birds, further human cases are likely," said Ian Wilson, a Scripps Research professor of molecular biology and head of the laboratory that conducted the recent study. "The potential for the emergence of a human-adapted H5 virus, either by re-assortment or mutation, is a clear threat to public health worldwide."

Of the H5N1 strains isolated to date, the researchers looked at A/Vietnam/1203/2004 (Viet04), one of the most pathogenic H5N1 viruses studied so far. The virus was originally isolated from a 10-year-old Vietnamese boy who died from the infection in 2004. The hemagglutinin (HA) structure from the Viet04 virus was found to be closely related to the 1918 virus HA, which caused some 50 million deaths worldwide.

Using a recently developed microarray technology -- hundreds of microscopic assay sites on a single small surface -- the study showed that relatively small mutations can result in switching the binding site preference of the avian virus from receptors in the intestinal tract of birds to the respiratory tract of humans. These mutations, the study noted, were already known in some human influenza viruses to increase binding for these receptors.

The study was published by ScienceXpress, the advance online version of the journal Science.

The study was careful to note that these results reveal only one possible route for virus adaptation. The study concluded that other, as yet "unidentified mutations" could emerge, allowing the avian virus to switch receptor specificity and make the jump to human-to-human transmission.

The work was supported by the National Institute of Allergy and Infectious Disease, the National Institute of General Medical Sciences and the National Institutes of Health.

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