Findings see bird flu link in pandemic 1918 virus

WASHINGTON -- The 1918 flu that killed 20 million people appears to be more like avian flu than previously thought, according to findings by US and British researchers that could help explain why it was the deadliest influenza strain ever recorded.

The work doesn't have direct implications for Asia's current outbreak of bird flu, a strain that doesn't seem able to easily infect many people.

But the findings, to be published today by the journal Science, do highlight how important it is to monitor avian flu -- because the research suggests it might take fewer genetic adaptations than once thought for a bird virus to begin spreading from person to person.

The research, conducted separately by scientists at the Scripps Institute in La Jolla, Calif., and at Britain's Medical Research Council, used lung samples preserved from victims of the 1918 flu to reconstruct a protein crucial to their infection.

"These were not little steps but big strides toward understanding, at the structural and molecular level, what it is about these strains that make them dangerous," said Dr. Gregory Poland, a flu specialist at the Mayo Clinic.

The findings don't completely explain the 1918 strain's virulence, cautioned Michael Perdue, who investigates avian flu at the Agriculture Department's Agricultural Research Service. Other factors than the protein studied, called hemagglutinin, play a role too, he said.

But "this would put together several pieces" of that puzzle, Perdue said. Also, "it suggests the potential is certainly there for rapid transition from an avian to a mammalian strain."

Different influenza strains spread around the world annually. Usually, they're similar to ones that have spread previously. Every so often, a new strain tough enough to kill millions emerges, and specialists believe the world is overdue for another pandemic. Unraveling the 1918 flu could help doctors better react if a similar strain returns.

All flu viruses are thought to have originated in birds. But scientists also have long thought that to cause human epidemics, the viruses first had to jump from birds to pigs, where genetic changes that allow the strains to better spread in mammals occur.

Flu strains that are more birdlike are more dangerous to people because their immune systems haven't been exposed to them before.

Asia's current bird flu, a strain known as H5N1, clearly can jump directly from poultry to people -- at least 16 people have died of it this winter. Most cases have been traced directly to contact with sick birds, although human-to-human transmission has not been ruled out in one instance.

In the new research, scientists reconstructed the three-dimensional structure of the hemagglutinin protein, a protein on the surface of the flu virus that allows it to attach to and penetrate lung cells.

Hemagglutinin from human and bird flu viruses interact with different cell receptors, which is why birds infecting people is rare.

But the new studies show the structure of hemagglutinin from the 1918 flu changed to make it capable of attaching to human cells, yet retained features primarily found in avian viruses, not human or pig strains.

The findings don't rule out a brief stop in pigs before the 1918 flu took off in people, said molecular biologist Ian Wilson, lead investigator of the Scripps team.

But "we want to know how many differences there have to be to an avian flu in order to infect the human," he added. The research suggests not all that many differences are required, if they're in the right spots.

The hemagglutinin from the 1918 virus is in a different family, called H1, than the H5-bird flu now affecting Asia, cautioned the lead British investigator, Sir John Skehel. The two "are quite different," he said, meaning the research won't have an immediate impact on the current bird flu. Still, the cell receptor properties found to have been key to the spread of the 1918 flu could point to molecular spots that need particular monitoring to predict when an outbreak of flu in poultry will prove more dangerous to people, Mayo's Poland said.