Mutant Flu Virus Could Hold Key to Fighting Bird Flu Pandemic

WASHINGTON — Government scientists say they have created mutant viruses that could help them understand how a human "bird flu" pandemic might start and how they might fight it.

Studying the mutated H5N1 viruses could open the door to more rapid vaccine development or even ways to come up with preemptive vaccines and antiviral drugs before a pandemic begins, they say.

The World Health Organization has confirmed that 319 humans have contracted H5N1 from contact with infected chickens, ducks and other fowl, and 192 of them have died.

The international organization says that so far, the virus has not spread from person to person. But if H5N1 mutates into a form that can do so, millions could die before a vaccine is ready, experts say.

Working with biochemists at Emory University in Atlanta, scientists at the National Institutes of Health have deliberately created mutant viruses that appear to have at least some of the physical characteristics of a virus that would spread in humans.

"While nobody knows if and when H5N1 will jump from birds to humans, (the researchers) have come up with a way to anticipate how that jump might occur and ways to respond to it," said Dr. Elias Zerhouni, director of the National Institutes of Health.

Dr. Anthony Fauci, director of the National Institutes of Allergy and Infectious Diseases, said, "Now we can begin, preemptively, to consider the design of potential new vaccines and therapeutic antibodies to treat people who may someday be infected with future emerging avian influenza virus mutants."

"This research could possibly help to contain a pandemic early on," he added.

The discovery is being reported Friday in the journal Science by a team led by Dr. Gary Nabel, head of vaccine research in Fauci's agency, and Dr. David Smith of the Emory School of Medicine.

Nabel explained in an interview that the key to human transmission apparently is found in a small portion of the molecules known as hemagglutinin that cover the surface of each flu virus. They account for the "H" in H5N1.

These molecules have a "canyon and ridge" shape that allows them to fit onto "spikes" that appear on the outside of human or bird cells, he said.

Once the virus locks itself to the human cell, it is able to go inside the cell and cause the cell to create millions of new influenza viruses, which then lock onto other cells.

Nabel said that deep in the bottom of the hemagglutinin canyon, different strains of influenza viruses have different molecular patterns. These differences seem to determine whether the hemagglutinin will lock onto the spikes of the victim's cells.

Except in the relatively small number of cases where people have gotten bird flu, hemagglutinin in H5N1 will not bind to the "spikes" on human cells, and slips off the cells.

Using genetic engineering, Nabel's group made changes in H5N1's hemagglutinin. The mutated viruses were then sent to Emory, which maintains a "library" of the molecules that appear on human cells.

The Emory group quickly established that the mutated viruses attached themselves to a particular human molecule — the kind found on the spikes on human cells.

Nabel said that he subjected the mutated virus to antibodies produced by vaccines designed to fight existing H5N1 viruses. The antibodies were 10 times less effective at neutralizing the mutant virus than the existing viruses, he said.

Nabel said his team needed to cause only two deliberate mutations to change H5N1 into a virus that would readily lock onto human cells. Nabel said that for H5N1 to mutate into a human disease, other mutations likely would have to occur as well.