Ram Sasisekharan, who is currently a professor of Biological Engineering and Health Sciences and Technology at the MIT Massachusetts Institute of Technology (MIT), says that the two mutations in the 1918 influenza strain occurred in a surface molecule called hemagglutinin (HA), which allowed it to bind tightly to receptors in the human upper respiratory tract.
"Two mutations dramatically change the HA binding affinity to receptors found in the human upper airways," said Sasisekharan.
In a previous research paper, Sasisekharan and his colleagues had suggested that flu viruses could only bind to human respiratory cells if they matched the shape of sugar (or glycan) receptors found on those cells.
The glycan receptors found in the human respiratory tract are known as alpha 2-6 receptors, and they come in two shapes-one resembling an open umbrella, and another resembling a cone.
That time, the research team said that avian flu viruses must gain the ability to bind to the umbrella-shaped alpha 2-6 receptor to infect humans.
In their current study, they have found that two mutations in HA allow flu viruses to bind tightly or with high affinity to the umbrella-shaped glycan receptors.
"The affinity between the influenza virus HA and the glycan receptors appears to be a critical determinant for viral transmission," said Sasisekharan.
With a view to investigating the biochemical basis for hemagglutinin binding to glycans, which leads to viral transmission, the researchers used the 1918 influenza virus as a model system.
They compared the virus that caused the 1918 pandemic (known as SC18) with a strain called NY18 that differs from SC18 by only one amino acid, and also the AV18 strain, which differs from SC18 by two amino acids.
The research team found that NY18, which is only slightly infectious, binds to the umbrella-shaped alpha 2-6 receptors but not as well as SC18, which is highly infectious.
They also observed that AV18, which does not infect humans, does not have any affinity for the umbrella-shaped alpha 2-6 receptors, and binds only to alpha 2-3 receptors.
The researchers also revealed that another strain called TX18 binds to alpha 2-6 and alpha 2-3, and is much more infectious than NY18 because it binds with high affinity to the umbrella-shaped alpha 2-6 receptors.
The researchers claim that their study, published in the journal Proceedings of the National Academy of Sciences, is the first to explain the exact biochemical reasons underlying the varying infectiousness of these strains, which they reported last year.
They believe that their work may facilitate the monitoring of the HA mutations in the H5N1 avian flu strains currently circulating in Asia. According to them, such mutations may enable the virus to jump from birds to humans, as many epidemiologists fear will occur.