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2022-8-8 5:37:49

Study finds mutations needed for bird flu pandemic
submited by kickingbird at Mar, 17, 2006 14:17 PM from Reuters

Scientists said on Thursday they had identified some of the mutations the H5N1 avian influenza virus needs to gain a permanent foothold in the human population, causing a greatly feared pandemic.

They said the test they used, called a glycan microarray, might be useful in monitoring the virus in birds and as it infects people, to see if it is mutating into a form that would allow it to pass easily from person to person.

H5N1 has moved steadily across Asia and into Europe since it reappeared in 2003, and has picked up speed in recent weeks. It has killed just over 100 people but remains mostly a virus of birds.

No one can predict when, or even if, it will evolve into a form that transmits easily from one person to another, but fears are that it will. Scientists have been examining the virus when they can get samples and trying to predict just which changes are needed to make it change from a bird-specific to a human-specific form.

Ian Wilson and a team at The Scripps Research Institute in La Jolla, California looked at a structure on the surface of all influenza viruses called hemagglutinin. It is the "H" in H5N1 and there are 16 known types of hemagglutinin.

Only three -- H1, H2 and H3 -- have been known to cause human disease and they caused the last three great influenza pandemics, in 1918, 1957 and 1968.

"When pandemics start, we really don´t know, with the first virus that enters the human population, how well it is adapted to humans," Wilson said in a telephone interview.

Working with flu experts Terence Tumpey of the Centers for Disease Control and Prevention in Atlanta and Jeffery Taubenberger of the Armed Forces Institute of Pathology in Rockville, Maryland, Wilson´s team dissected and imaged a sample of influenza virus that killed a 10-year-old Vietnamese boy in 2004.


They found its hemagglutinin looked very similar to the virus that caused the 1918 pandemic, which killed anywhere between 50 million and 100 million people. It looked less similar to H5N1 taken from a duck in Singapore.

"Of the H5N1 viral isolates studied to date, A/Vietnam/1203/2004 (Viet04) is among the most pathogenic in mammalian models, such as ferrets and mice," the researchers wrote in their report, published in the journal Science.

Hemagglutinin allows the virus to attach to the cells it infects, and it has to be able to grapple a structure called sialic acid, which is slightly different in different animal species.

So to pass from birds to humans, the virus must mutate enough to allow it to bind to, for instance, both a human lung cell and a chicken´s intestinal cell.

Wilson´s team identified a structure that, in the human configuration, is called an alpha 2-6 receptor and in birds an alpha 2-3 receptor. It must change from the bird to human configuration, they found, to cause human epidemics.

This "critical step ... appears to be one of the reasons why most avian influenza viruses, including current avian H5 strains, are not easily transmitted from human-to-human following avian to human infection," they wrote.

Earlier studies had shown it took only two changes to make the 1918 virus look just like a purely avian virus. That may suggest it may not take much mutation to change a bird virus into a human pandemic strain.

The test may help monitor for these changes, Wilson said.

"This test that you can do for receptor testing specificity, this glycan array, is something you could possibly think about using in the field," Wilson said.

So if the virus has not mutated yet, why does it ever infect people? "It´s not an all or nothing," Wilson said.

"It´s a preference. At higher doses, doses that normally you and I wouldn´t pass the virus on to one another... you can overcome this (species) barrier."
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