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2022-8-20 1:00:11


2 Mutations Were Critical to Spread of 1918 Flu (HealthDay)
submited by 2366 at Feb, 20, 2008 1:33 AM from Yahoo News

TUESDAY, Feb. 19 (HealthDay News) -- New research on the spreadof the 1918 influenza virus, which killed more than 50 million peopleworldwide, may aid research into today´s potentially dangerous bird flustrain, scientists say.

MIT researchers found that the 1918 avian flu virus strain developedtwo mutations in a surface molecule called hemagglutinin (HA), whichallowed it to bind tightly to receptors in the human upper respiratorytract. This ability to "lock in" was critical for viral transmission inhumans, according to the findings, published in Feb. 18 issue of theProceedings of the National Academy of Sciences.

"Two mutations dramatically change the HA binding affinity to receptorsfound in the human upper airways," said the paper´s senior author RamSasisekharan, the Underwood Prescott Professor of Biological Engineeringand Health Sciences and Technology, in a prepared statement.

Sasisekharan and colleagues previously reported in January´s NatureBiotechnology that flu viruses can only bind to human respiratorycells if they match the shape of sugar (or glycan) receptors found onthose cells. The receptors, known as alpha 2-6 in humans, come in twoshapes -- one resembling a cone; the other an open umbrella.

In the new study, the team discovered that for avian flu viruses totransmit from birds to humans, they must gain the ability to bind tightlyor with a high affinity to the umbrella-shaped receptors.

"The affinity between the influenza virus HA and the glycan receptorsappears to be a critical determinant for viral transmission," Sasisekharansaid.

The researchers compared the influenza virus that caused the 1918pandemic with two similar strains (called NY18 and AV18) that differ fromit by only one or two amino acids.

Using ferrets (which are susceptible to human flu strains), researchershad earlier found that the pandemic virus transmitted efficiently betweenferrets, while the NY18 strain proved only slightly infectious and AV18not at all infectious.

While slightly infectious NY18 binded to the umbrella-shaped glycanreceptors, it did not do it as well as the highly infectious pandemicstrain did. The non-infectious AV18 strain had no affinity for thereceptors.

Another strain, TX18, proved much more infectious than NY18, and itbonded with high affinity to the umbrella-shaped receptors.

Researchers from the Centers for Disease Control and Preventionreported on the infectiousness of these strains last year, but the MITstudy is the first to explain the biochemical reason causing thesedifferences.

More information

The U.S. Centers for Disease Control and Prevention has more about influenza.

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