Glycobiology Sugars and Influenza (Flu)

Larry A. Law

Glycobiology involves the study of eight sugars within the human body. These sugars (glycans) form antenna structures called cell receptors on the surface of all cells. One of the most important sugars is called sialic acid. It is often located at the end of these antennas. Sialic acid is made from another sugar called mannose within the body. The influenza virus attaches to human cells via sialic acid. The geometry of the sugar connection determines whether flu from animals can infect humans. The current coronavirus pandemic thought to originate from bats is a good example. Avian (bird) flu prefers to bind to sialic acid which is attached to galactose via an alpha (2,3) link (the second carbon in sialic acid is linked to the third carbon in galactose). Human flu prefers an alpha (2,6) link (sixth carbon in galactose). 

Studies of flu pandemics from 1918, 1957, 1968, and 2009 suggest these viruses successfully mutated from the alpha (2,3) link (animal) to the alpha (2,6) link (human). The 1918 flu resulted in 35 million deaths. This was more deaths than from World War I and World War II combined! Understanding glycobiology and how glycans are employed on cells is critical for prevention efforts and disease treatments involving drugs or vaccines.

These sugars studied  in the science of glycobiology have existed in nature since the dawn of time. Our body’s immune systems are synchronized to the tiniest variation in the geometry of cell-surface, sugar-structures. Glycobiology represents the frontier for understanding disease and metabolic processes in the body.

A good example of how these sugars are being recognized involves the Centers for Disease Control (CDC). The CDC comes up with names for different influenza using a labeling system focused on these sugars. Let's consider the H5N1 label. H stands for hemagglutinin which is a protein that binds/attaches the virus to sialic acid receptors on the surface of human cells. This attachment allows the virus to enter the targeted cell. N stands for neuraminidase which is the enzyme that cleaves or cuts the connection to sialic acid. When the newly formed virus emerges out of the infected cell it is attached to a cell receptor. The enzyme cleaves the sialic acid attachment which frees the virus to travel to another non-infected cell and begin the process all over again. Epithelial cells of swine trachea produce both alpha (2,3) and alpha (2,6) linked sialic acids. It is theorized that avian flu with the alpha (2,3) link is morphed into a human binding alpha (2,6) linkage within swine.  The swine serve as the mixing vessel for new pandemic type viruses. Because of the importance of this type of receptor for flu, the CDC actually tracks this specific glycobiolody linkage on these sugars as it watches for the next potential epidemic.
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While there is not much we can do to avoid a pandemic virus, the best defense is still a strong immune system. If you would like to see the class where we overview critical sugar nutrients and how they strengthen our immune system click here.