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What is Influenza Hemagglutinin?

By Heather Scoville
Updated May 17, 2024
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Influenza is a disease caused by the influenza virus. Viruses are known agglutinates of red blood cells, which means they cause the cells to clump together. Influenza hemagglutinin (HA) is attached to the surface of the influenza virus and is responsible for the binding of the virus to the host cell.

Each influenza virus has a receptor complex on its surface comprised of influenza hemagglutinin and neuraminidase (NA). While the hemagglutinin allows the virus to anchor to and enter the host cell, the neuraminidase gets a reproduced virus out of a cell so it can infect a different one. Each type of influenza has a hemagglutinin and a neuraminidase combination specific to that type.

Hemagglutinin is a trimer protein; it is composed of three regions. The influenza hemagglutinin is made up of monomers called HA1, HA2 and HA3. They are arranged into two domains called the globular domain and the stem domain. Slight differences in the stem domain structure create different types of hemagglutinin.

There are 16 types of influenza hemagglutinin. Each type is named with the letter “H”, followed by a number. Similarly, there are nine known neuraminidases named with the letter “N” followed by a number. H1, H2, and H3 can be paired with N1 or N2 in humans. Different strains of the influenza virus are named for their hemagglutanin and neuraminidase combinations, like H1N1.

The combination of the influenza hemagglutinin and neuraminidase determines the seriousness of that particular strain of influenza. H5N1, also known as the avian or bird flu, is a particularly deadly strain of the disease since the H5 hemagglutinin is not usually found in humans. The H5N1 strain must first mutate one amino acid in its protein before it can integrate into human cells. Once a human is infected with H5N1, the disease quickly takes over and may be lethal.

Researchers believe the key to treating influenza is to figure out how to block the influenza hemagglutinin from binding to the host cell. Since the hemagglutinin is responsible for the virus getting into the healthy cell, it makes a potential target when fighting the disease. Vaccines can be produced to block the influenza hemagglutinin from binding to the cell receptor, making it impossible for the virus to invade the cell.

Some types of antibodies are moderately successful at inhibiting influenza hemagglutinin from binding to a cell. These neutralizing antibodies work in one of two ways. A few antibodies can attach to the stem domain and prevent the virus from fusing to the cell membrane where it enters. Most neutralizing antibodies will bind to the globular domain and block interaction with the cell receptor.

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