Fowl fears: There's no sign that the H5N1 virus, which has spread to Africa and Europe, has become more dangerous to people. Credit: REUTERS/George Esiri

Fears of a bird flu pandemic heightened in January when scientists reported that samples of H5N1 taken from infected individuals in Turkey carry mutations that could enable the virus to spread more easily among people. But experts now say the news may have raised red flags prematurely.

“Some of the initial enthusiasm for the results may have been overinterpreted,” says Alan Hay, director of the World Health Organization (WHO) collaborating laboratory in London that is analyzing samples from Turkey and Iraq. “It's not apparent that these [genetic] differences have a dramatic impact on pandemic potential.”

Some of the initial enthusiasm for the results may have been overinterpreted. Alan Hay, WHO

Hay and others say that because mutations are a defining feature of the influenza virus, it is not surprising that researchers found tiny genetic differences between the Turkish H5N1 samples and other strains of the virus.

Carrying RNA instead of DNA, influenza viruses mutate constantly because the enzyme that generates RNA makes frequent mistakes during replication. But scientists say it's unlikely that just one or two genetic reshuffles could give rise to a complex and potentially lethal virus that is fully adapted to humans.

“These viruses have ten different genes and eight different pieces of RNA which all have to work together and evolve together and mutate together and adapt together,” says Michael Perdue, a senior scientist with the WHO's Global Influenza Program. “One change doesn't automatically mean a new virus.”

Still, one of the three Turkish mutations, noted before in Hong Kong and Vietnam, worried researchers. The change is an amino acid substitution in hemagglutinin—the 'H' of H5N1—a key surface protein that enables the highly pathogenic virus to invade foreign cells.

“This is an important observation and a worrying one that the virus is more able to associate with human receptors and human cells,” says Robert Webster, a virologist at St. Jude Children's Research Hospital in Tennessee. Due to the virus' inherent propensity to change, however, Webster adds that public health authorities must adopt a wait-and-see approach, acting only when human-to-human transmissions start to appear.

That hasn't happened yet. Nearly all 161 human cases of avian flu thus far have resulted from direct exposure to wild or domestic infected birds.

Meanwhile, researchers are trying to pinpoint why some H5N1 mutations are more virulent then others. Taking a big step in that direction, bioinformaticist Clayton Naeve in January released sequence information for 169 strains of avian influenza and 2,196 additional avian flu genes, effectively doubling the available information on avian flu strains (Science doi:10.1126/science.1121586).

“All of these traits we speak about, like transmissibility and virulence, are multigenic traits,” says Naeve, who used duck, poultry and other avian viral strains stored in a vast viral repository maintained by Webster. “With a more detailed analysis of this huge new amount of genetic data, we will have a better ability to understand multigenic traits for the first time.”

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