2 Mutations Were Critical to Spread of 1918 Flu

TUESDAY Feb. 19, 2008 -- New research on the spread of the 1918 influenza virus, which killed more than 50 million people worldwide, may aid research into today's potentially dangerous bird flu strain, scientists say.

MIT researchers found that the 1918 avian flu virus strain developed two mutations in a surface molecule called hemagglutinin (HA), which allowed it to bind tightly to receptors in the human upper respiratory tract. This ability to "lock in" was critical for viral transmission in humans, according to the findings, published in Feb. 18 issue of the Proceedings of the National Academy of Sciences.

"Two mutations dramatically change the HA binding affinity to receptors found in the human upper airways," said the paper's senior author Ram Sasisekharan, the Underwood Prescott Professor of Biological Engineering and Health Sciences and Technology, in a prepared statement.

Sasisekharan and colleagues previously reported in January's Nature Biotechnology that flu viruses can only bind to human respiratory cells if they match the shape of sugar (or glycan) receptors found on those cells. The receptors, known as alpha 2-6 in humans, come in two shapes -- one resembling a cone; the other an open umbrella.

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

"The affinity between the influenza virus HA and the glycan receptors appears to be a critical determinant for viral transmission," Sasisekharan said.

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

Using ferrets (which are susceptible to human flu strains), researchers had earlier found that the pandemic virus transmitted efficiently between ferrets, while the NY18 strain proved only slightly infectious and AV18 not at all infectious.

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

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

Researchers from the Centers for Disease Control and Prevention reported on the infectiousness of these strains last year, but the MIT study is the first to explain the biochemical reason causing these differences.

More information

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

Posted: February 2008


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