Flu Sequence Offers Clues to Deadly Virus

Although the Hong Kong "bird flu" has killed six people--the latest died yesterday--and prompted the slaughter of 1.5 million chickens, it remains largely a mystery to scientists. Now a team from the United States and Hong Kong has taken the most detailed look yet at the virus's genes. Although the scientists cannot yet explain the virus's jump from birds to humans, the partial sequence, reported in tomorrow's issue of Science, offers a clue about why the virus can be such an efficient killer.

This particular virus was isolated from a 3-year-old boy in Hong Kong, who died in May after coming down with a flulike disease that did not match any of the known human influenza strains (Science, 12 September, p. 1600). It did, however, match a bird strain, called H5N1 because of the varieties of the proteins hemagglutinin and neuraminidase on its surface. The finding triggered a public health alarm: Because there was no record of the bird strain infecting people, no one would have immunity to it, and epidemiologists feared it might trigger a pandemic.

By analyzing the DNA sequence of the virus, researchers led by Kanta Subbarao of the Centers for Disease Control and Prevention in Atlanta have uncovered what may be a clue to the strain's deadliness. When they sequenced the gene for hemagglutinin, they found an insertion next to a crucial spot where cellular enzymes of the host help break apart the virus's protein coat, allowing the virus to infect cells. In birds, the enzymes that cleave the protein are most concentrated in digestive and respiratory systems, so most flu strains can only infect those cells, says team member Michael Perdue of the U.S. Department of Agriculture's Southeast Poultry Research Laboratory in Athens, Georgia. But the insert may provide an easier--and less specific--target for enzymes, allowing the virus to infect the heart, brain, and blood vessels. It's not clear whether the virus works the same way in humans, however.

In fact, the scientists are still unsure exactly how this flu strain manages to infect humans at all. To solve that question, Subbarao says, researchers are closely examining a range of avian flu viruses, hoping to pinpoint how this H5N1 strain is different. However the virus has altered to allow bird-to-human infection, it doesn't seem to pass easily between humans. So far, there has been only one suspected case of transfer from one person to another.

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