Scientists Discover New Key to Flu Transmission

Flu viruses must be able to break a very specific code before it can enter and infect human respiratory cells, U.S. researchers said on Sunday, presenting a new understanding of how influenza works.

This discovery may be able to offer scientists a better way to monitor changes in the H5N1 bird flu virus that could possibly trigger a deadly pandemic in humans. It may also lead to better ways to fight it as well.

Scientists found that a flu virus must be able to attach itself to an umbrella-shaped receptor covering human respiratory cells before it can infect the cells of the upper airways. Ram Sasisekharan, a professor of biological engineering and health sciences at Massachusetts Institute of Technology in Cambridge, said “What the lock needs is the right key. It opens the door.”

Experts fear that the bird flu virus, which almost exclusively affects birds, may evolve slightly into a form that people can easily catch and pass to one another, which may in turn trigger an epidemic.

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

Before the virus can enter a human respiratory cell, a protein on the surface of the virus has to bind with links of sugars called glycans that rest on the outside of the cells. Scientists have classified these links according to how they are linked together chemically. In birds, the virus binds with alpha 2-3 receptors, however in humans, it binds with alpha 2-6 receptors.

Scientists first believed that in order to infect humans, the H5N1 bird flu virus would need to simply mutate to bind to the alpha 2-6 receptors. But it turned out that not all alpha 2-6 receptors are the same. "Defining human and bird receptors just by linkage forgets to take shape into account," Sasisekharan said in a telephone interview.

Shape difference may explain why humans can get the bird flu from a bird and not pass it on to other humans easily. So far, the bird flu virus has only been able to attach and bind to cone-shaped structures rather than umbrella-shaped structures in human upper airways.

According to the World Health Organization, the virus has already killed 216 people and infected 348 people in 14 countries.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 observation 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.