Bird Flu Gene Analysis Finds New Clue

WASHINGTON - Scientists who have made a big leap in unraveling the genetic code of bird flu viruses along the way found a new clue that may help explain why the notorious H5N1 strain is so deadly.

St. Jude Children's Research Hospital in Memphis, Tenn., is home to a remarkable viral library, samples of about 11,000 influenza viruses that Dr. Robert Webster has gathered from around the world since 1976. They're not just flu viruses that have infected people over the years, but ones from pigs and other animals — including about 7,000 bird flu viruses, gathered from poultry, ducks, gulls and other flocks.

Thursday, St. Jude researchers reported in the journal Science that they have completed the first large genetic analysis of more than 300 of these bird flu viruses. They identified 2,196 bird flu genes and 160 complete genomes, doubling the amount of genetic information available for scientists to study how these viruses evolve and spread over time.

Simply having that new trove of gene information — posted in a public genetic database so that any scientist can mine it — in itself is a huge step, said Dr. Maria Giovanni of the

National Institutes of Health, which has launched a major project to map influenza genomes and helped to fund the St. Jude's work. So far, most of the complete influenza genomes available are from human viruses.

Until now, scientists trying to decode flu genetics have mostly focused on specific genes involved in making flu vaccines, such as hemagglutinin — the H in H5N1 — on the virus' surface that triggers the immune system to mount an attack. Encounter a brand new hemagglutinin variation, like when H5 strains first infected people in 1997, and the body doesn't know how to defend itself.

But unique hemagglutinin alone doesn't explain why H5N1 is so dangerous to people.

Decoding all the influenza genes instead of select ones will help scientists learn how these constantly evolving viruses change and spread, and why some are so much more virulent than others.

Enter the new clue, a protein called NS1 produced inside flu-infected cells. In bird flus, the NS1 protein harbors a molecular feature that seems to help the virus latch onto and disrupt certain important cellular processes — a feature that influenza strains common in humans don't seem to have, the researchers concluded.

"It's likely to be important in virulence, but we don't have any evidence that it's the case yet," cautioned St. Jude's Dr. Clayton Naeve, who led the new research.

But if the finding pans out, it might provide a marker of virulence. That would be very useful for scientists who collect samples of emerging flu viruses and today struggle to predict which might prove unusually dangerous, explained Dr. Karen Lacourciere, a flu specialist with NIH's National Institute of Allergy and Infectious Disease.

Probably there will be multiple factors that determine a virus' virulence, she stressed.

"If you can help detect factors that correlate with virulence, it helps us in ... understanding when we see a virus whether it's one we should be more concerned about," she said.