Scientists discover new key to flu transmission

CHICAGO Flu viruses must be able to pick a very specific type of lock before entering human respiratory cells, U.S. researchers said on Sunday, offering a new understanding of how flu viruses work.

The discovery may help scientists better monitor changes in the H5N1 bird flu virus that could trigger a deadly pandemic in humans. And it may lead to better ways to fight it, they said.

The scientists found that a flu virus must be able to attach itself to an umbrella-shaped receptor coating human respiratory cells before it can infect cells in the upper airways.

"What the lock needs is the right key. It opens the door," said Ram Sasisekharan, a professor of biological engineering and health sciences at Massachusetts Institute of Technology in Cambridge.

The H5N1 avian flu virus now almost exclusively infects birds. But it can occasionally pass to a person.

Experts have feared that the bird flu virus would evolve slightly into a form that people can easily catch and pass to one another, triggering an epidemic.

"We now know what to look for," said Sasisekharan, whose study appears in the journal Nature Biotechnology.

Before a flu virus can enter a human respiratory cell, a protein on the surface of the virus must bind with chains of sugars called glycans that sit on the outside of the cells.

Scientists have classified these chains according to how they are linked together chemically. In birds, the virus binds with alpha 2-3 receptors; in humans, it binds with alpha 2-6 receptors.

To infect humans, scientists thought the H5N1 bird flu virus would need to simply mutate so it could bind with alpha 2-6 receptors. But it turns out not all alpha 2-6 receptors are the same. Some are short and cone-shaped and some are long and umbrella-shaped.

"Defining human and bird receptors just by linkage forgets to take shape into account," Sasisekharan said in a telephone interview.

VIRUS SURVEILLANCE

Shape difference may explain why humans can get bird flu from a bird and not pass it along easily to other humans, he said.

So far, the bird flu virus has found a way to bind only to the cone-shaped structures in human upper airways. The virus has already killed 216 people and infected 348 people in 14 countries, according to the World Health Organization.

But the study found that the most infectious human flu viruses bind with the umbrella-shaped receptors in the upper respiratory tract. The researchers believe the H5N1 bird flu virus would need to adapt so it could latch on to these umbrella-shaped receptors before it could be spread readily from human to human.

Understanding this mechanism could lead to better surveillance of changes in the virus and may lead to the development of new and better drugs to treat flu viruses.

"It opens up ways for people to bring in different kinds of small molecule approaches for new drug development," Sasisekharan said, adding the work could help seasonal flu sufferers as well.

(Editing by Eric Beech)