Fascinating Aspects of Glycobiology—Part 5 (Influenza)

Larry A. Law

Attachment of the influenza virus to human cells requires sialic acid (one of the eight sugars). Avian (bird) flu prefers to bind to sialic acid attached to a galactose molecule via an alpha (2,3) link. Alpha (2,3) means that the second carbon atom in sialic acid is linked to the third carbon atom in galactose. Human flu prefers an alpha (2,6) link. Studies of flu pandemics from 1918, 1957, 1968, and 2009 suggest that these viruses successfully mutated from the alpha (2,3) link to the alpha (2,6) link. 

Mutations

Understanding glycobiology and how glycans are employed on cells is critical for prevention efforts and disease treatments. These sugars have existed in nature since the dawn of time. The body's immune system is 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. The Centers for Disease Control (CDC) monitor this alpha linkage in an effort to warn the public concerning these mutations that would make humans more vulnerable. 

Flu Names

The CDC comes up with names for different influenzas based on the following. For example, in the H5N1 label, H stands for hemagglutinin, a protein that binds/attaches the virus to sialic acid receptors on the surface of epithelial cells in the throat. This attachment allows the virus to enter the targeted cell. N stands for neuraminidase, the enzyme that cleaves (cuts off) sialic acid. When the newly-formed virus emerges out of the infected cell, it is attached to a cell receptor via sialic acid. The enzyme cleaves sialic acid, freeing the virus to travel to another non-infected cell and begin the process all over again. H5N1 is bird flu and H1N1 is swine flu, but there are multiple numbered categories with which to identify various flu viruses. H1N1 generally spreads easily, but is rarely fatal. H5N1 spreads slowly, but is more often fatal.

Pig/Swine Flu

Epithelial cells of swine trachea have both alpha (2,3) and alpha (2,6) linked sialic acid. Scientists theorize that avian flu with the alpha (2,3) link morphs 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 linkage on these sugars to watch for the next pandemic virus.