Either of two simple bird flu virus mutations could trigger a deadly pandemic, Japanese scientists warn.
Both mutations already have popped up in humans infected with the H5N1 bird flu virus.
They've been seen in bird flu viruses isolated from two people in Azerbaijan and from one person in Iraq, according to the Japanese scientists. Neither mutation has been seen among the more than 600 H5N1 viruses isolated from birds.
The two human mutations give the bird flu virus the ability to attach to human cells. It's the kind of mutation seen early in the 1918, 1957, and 1968 flu pandemics, warn Shinya Yamada of the University of Tokyo and colleagues.
Fortunately, the H5N1 viruses carrying these mutations do not appear to have caused any outbreaks of human-to-human transmission.
But these mutants seem capable of replicating in humans -- "an essential indicator of pandemic potential," the researchers report.
Flu viruses attach to receptor molecules on the outside of cells that line the airway.
Bird flu viruses use a receptor called SAalpha2,3Gal. Human flu viruses use a closely related receptor called SAalpha2,6Gal.
Previous flu pandemics came from bird flu viruses. Each time, the pandemic took off when the viruses learned to attach to human airway cells.
Yamada and colleagues manipulated H5N1 viruses in the laboratory to see what it would take to make a bird flu virus do this. They found that either of two mutations -- single amino-acid changes at specific places in the viral DNA -- did the trick.
The researchers suggest that health authorities look for these mutations in bird flu viruses isolated from humans. If found, they could be an early warning of a budding pandemic.
Yamada and colleagues report their findings in the Nov. 16 issue of the journal Nature.
By Daniel J. DeNoon, reviewed By Louise Chang, MD
SOURCE: Yamada, S. Nature, Nov. 16, 2006; vol 444: pp 378-382.