Hemagglutinin (HA) and neuraminidase(NA)

Hemagglutinin (designated as HA) and neuraminidase (designated as NA) are glycoproteins. Hemagglutinin and neuraminidase protrude from the outer surface of the influenza virus and neuraminidase is a constituent of the enveloping membrane that surrounds the viral contents. A glycoprotein is a protein that contains a short chain of sugar as part of its structure. The hemagglutinin and neuraminidase glycoproteins are important in the ability of the virus to cause influenza.

A typical influenza virus particle contains some 500 molecules of hemagglutinin and 100 molecules of neuraminidase. These are studded over the surface of the virus.

The illness caused by the influenza virus can be devastating. For example, in 1918 a new genetic variant of the virus swept around the world and in just over a year over 20 million people succumbed to the influenza. The variation was due to alterations in both the hemagglutinin and neuraminidase components of the virus. Further antigenic variations of these molecules produced a virus that, at least for some time, was not recognized by the immune system . The result was localized outbreaks or worldwide outbreaks in 1957, 1962, 1964, 1976, and 1978.

Hemagglutinin derives its name from its activity. The glycoprotein confers upon the virus the ability to agglutinate, or clump together, red blood cells. The aggregation compromises the function of the red blood cells. The hemagglutinin glycoprotein also functions in the binding of the virus to cells, via the recognition of a chemical structure on the cells surface called sialic acid. The binding of hemagglutinin to sialic acid compounds on the surface of cells is the initial event in the association of the virus with human epithelial cells. These two activities associated with hemagglutinin are important activities in the infectious ability of the virus. Indeed, hemagglutinin is the major virulence (disease-causing) factor of the influenza virus.

There are three distinct haemagglutinins important in human infections that are encoded by genes in the virus. These are designated as H1, H2, and H3. Animal influenza viruses contain nine additional types of hemagglutinin.

Neuraminidase is the common name for acetyl-neuraminyl hydrolase. The glycoprotein compound is an enzyme. The enzyme removes residues called N-Acetyl-neuraminic acid from chains of sugars and from other glycoproteins. The disruption of the neuraminic acid residues allows the virus to both pass out of the human epithelial cells in which it is replicating, and enter new cells to initiate a new round of viral replication. The activity of neuraminidase disrupts the mucous fluid that is present in the respiratory tract. Also, possession of neuraminidase keeps the viruses from aggregating with other virus particles. The result of these activities is to ease the spread of the virus through the respiratory tract.

Two different species of neuraminidase, designated N1 and N2, are important in human infections, while seven additional species are important in animal influenza viruses.

Inhibitors of neuraminidase have been developed in an effort to thwart the viral infection. The inhibitors are structurally similar to the silica acid on the surface of human epithelial cells. The rational is that the virus will bind to the inhibitor rather than to the human cells, and the inhibitor-viral complex can be removed from the body.

Hemagglutinin and neuraminidase are used in the designation of the different antigenic types of the influenza virus that have and continue to appear. For example, Influenza A/Taiwan/86/H1N1 is an influenza A strain of the H1 hemagglutinin type and N1 neuraminidase type that was first isolated in Taiwan in 1986.

Both hemagglutinin and neuraminidase tend to undergo what is termed antigenic drift, which is a slight but frequent change in the antigenic character. The slight change is still usually enough to thwart the recognition capabilities of the immune system. Hence, annual vaccinations are necessary to minimize the chance of acquiring an influenza infection. A major antigenic change in one or both of the glycoproteins, as happened in the 1918 virus, is termed antigenic shift.

See also Flu, the great flu epidemic of 1918; Mutations and mutagenesis