Scientists Spot Potential Bird-Flu Pathwa

A mutation in a surface protein might lead to a pandemic, study says

A newly developed molecular technology has identified certain mutations that the avian flu virus might undergo to unleash a human epidemic, researchers report.

The key is a mutation in the hemagglutinin molecule -- the "H" in the H5N1 designation of the bird flu virus -- that sits on the surface of the virus and is the primary target of the immune system's protective antibodies.

Besides giving insight into just how H5N1 might change, the finding could help scientists recognize important viral mutations early on and alert health officials to the potential for a pandemic.

"We looked at the structure of the H5 hemagglutinin from a recent bird flu isolate in Vietnam," said Ian A. Wilson, professor of molecular biology at the Scripps Research Institute, in La Jolla, Calif. That virus, which was found in a boy who died of bird flu in 2004, was similar to the one that caused the 1918-19 "Spanish flu" pandemic, which killed an estimated 20 million to 40 million worldwide, he said.

"Although this is an avian [bird] virus, similar to the 1918 virus, what we are really looking at is how a virus crosses the species barrier," Wilson said.

In principle, it's a substantial barrier. The bird flu virus attaches itself to cells in the intestinal tract, while the human flu virus attacks cells in the respiratory tract.

However, a previous study showed that only two mutations were needed to transform the bird virus to one that could infect humans, Wilson said.

"Biologists are concerned about being able to detect changes in the avian virus that might signal a transition to moving to a human host," added James C. Paulson, another professor of molecular biology at Scripps. "This method specifically looked at one change known to be a major difference between the avian virus and its counterpart in humans."

As reported in the March 17 issue of Science, the researchers used a technique called functional glycan microarray, which studies specific sugar molecules that allow the virus to attach itself to cells. There are a few known mutations that can convert other viruses with H2- and H3-type components from bird to human infections, but the new study showed that these mutations do not cause the H5 bird flu virus to switch to a preference for infecting human cells.

There was a slight change in the virus found in the Vietnamese boy. "This paper concludes that this change might be sufficient for the avian virus to get a foothold in the human population, but not sufficient for the virus to have full virulence in humans," Paulson said.

Human infection with the avian virus currently requires direct exposure to infected birds, he noted.

According to James Stevens, an assistant professor of molecular biology at Scripps, the new research has "identified a possible route that the virus could take [in the future] to become adapted to human beings."

There is some comfort in an indication that this change might not be easy for the virus, Paulson added.

The functional glycan microarray technique was developed at Scripps and is being used by some other laboratories, Paulson said. It could be very useful in the continuing effort to determine whether and how the H5N1 avian flu virus might become a major menace to humans, he said.

"We don't know how well-adapted these viruses need to be to get a human foothold," Wilson pointed out. "I suggest that there could be tests in the field for receptor binding."

The bulk of bird-flu infections have occurred in Asia, although the germ has been identified in birds in Africa, Europe and the Middle East. More than 100 people have been killed by H5N1, which so far has only been caught through direct contact with infected birds.

 

TTFN