People infected with the H5N1 bird flu virus in Vietnam and Thailand had the "avian" version of the flu virus, as did the victims of the 1918 influenza pandemic, which killed tens of millions of people globally, the researchers said.

But the influenza viruses that cause the normal seasonal human misery, and those that caused the less deadly 1957 and 1968 human flu pandemics, do not carry the avian genes.

The finding, published in the journal Science, may provide a way to identify the more dangerous viruses and may also help companies trying to make better flu drugs, said St. Jude's Clayton Naeve.

"We documented a clear difference between bird viruses and human viruses. You need much more work to demonstrate this actually contributes to virulence in nature," Naeve said in an interview.

Naeve and his colleagues have been working to sequence the genomes of all known influenza viruses. No one has done this, even though flu viruses have just eight genes and are relatively simple organisms, the researchers said.

"This is information we expect will be very important in understanding the attributes of this virus -- how it will cross from birds to humans. We are releasing this data so that other investigators worldwide can mine it for information," he said.

VIRUS COLLECTION

The researchers used a collection of samples of 11,000 influenza viruses, including 7,000 avian influenza viruses, assembled by St. Jude's Dr. Robert Webster over 30 years.

"We have sequenced a diverse sampling of 336 avian influenza viruses from this collection including isolates from ducks, gulls, shorebirds and poultry collected in North American, Eurasian, and Australasian countries, primarily during the years 1976 to 2004," the researchers said.

The H5N1 virus has been found in birds for decades but it first was seen to infect people in 1997, in Hong Kong. Since it resurfaced in 2003, it has infected at least 152 people and killed 83 of them, according to the World Health Organization.

It has killed or forced the culling of hundreds of millions of birds.

H5N1 does not yet pass easily from person to person but experts fear it will mutate into a form that does so, sparking a pandemic that could kill millions or tens of millions.

One factor will be just what genetic changes the virus makes, and no one can predict what they will be.

But Naeve's team may have identified a protein to watch. It is called NS, for non-structural protein, and is only made once the virus has infected a cell.

The avian versions seem to allow the virus to do much more damage to a cell than the human versions of NS, Naeve said.

"We were surprised to see a lot of variation in this NS protein. That was the clue. We felt it must be playing an important biological role," he said.

It is possible that a mutation that would allow a flu virus to more easily infect people will weaken the NS protein, Naeve said. But no one knows.

"As time progresses one might expect that signature to change into a less-virulent form," he said, or it may not, as was apparently the case in 1918.