Hemagglutinin is a protein found on the outer surface of the influenza virus. It is integral to the virus’s ability to produce illness, acting as a kind of master key that allows the virus to gain access to an organism’s cells. This protein is a primary focus for scientists studying how the flu virus functions and for those developing annual vaccines.
The Role of Hemagglutinin in Infection
The primary function of hemagglutinin (HA) is to initiate infection by attaching the virus to a host cell. This protein is composed of a head and a stalk region, which work together to accomplish this task. The globular head of the HA protein is specifically structured to recognize and bind to certain molecules on the surface of cells in the human respiratory system.
This binding process is the first and most direct step in the viral life cycle. The HA head attaches to sialic acid receptors, which are common on the surface of epithelial cells lining the lungs and airways. This connection is often compared to a key fitting into a lock; the specific shape of the HA head must match the sialic acid receptor for the virus to latch on.
Once the virus is securely attached, the cell’s own machinery is tricked into engulfing the virus through a process called endocytosis. Inside the cell, the environment becomes more acidic, which triggers a dramatic change in the shape of the hemagglutinin protein. This conformational change involves the stalk region and causes the viral envelope to fuse with the cell’s membrane, releasing the virus’s genetic material into the host cell.
Hemagglutinin Subtypes and Naming Conventions
Scientists classify influenza A viruses based on two proteins on their surface: hemagglutinin (HA) and neuraminidase (NA). The different subtypes of hemagglutinin are identified by a number, such as H1, H2, or H3. Researchers have identified 18 different HA subtypes, primarily found in wild aquatic birds, which are a natural reservoir for a wide variety of influenza viruses.
The naming convention for an influenza A virus strain, such as A(H1N1), directly refers to the specific subtypes of these two proteins. The “H” in the name stands for hemagglutinin, while the “N” stands for neuraminidase, the other surface protein that helps new virus particles exit a host cell. This system allows researchers and public health officials to identify and track circulating strains.
While many combinations of HA and NA are possible, only a few subtypes have been found to circulate widely among humans. Currently, the dominant influenza A subtypes in the human population are H1N1 and H3N2. This classification is a tool in global surveillance, helping to monitor the viruses causing seasonal flu.
Hemagglutinin and Immune Response
When a person is infected with influenza or receives a flu vaccine, their immune system generates a targeted defense. A component of this defense is the production of antibodies, proteins that can recognize and neutralize the virus. The most effective of these are neutralizing antibodies, and they primarily work by targeting the hemagglutinin protein.
These neutralizing antibodies are effective because they bind to the globular head of the HA protein. By binding to the HA head, the antibodies physically obstruct this site, preventing the virus from latching onto the sialic acid receptors on respiratory cells.
This blocking action stops the infection before it can begin. This mechanism of neutralization is a primary goal of vaccination, as stimulating the production of these specific antibodies provides protection against future infection by the same or a very similar viral strain.
Viral Evolution and Vaccine Development
The constant pressure from the human immune system drives the evolution of the influenza virus, particularly its hemagglutinin protein. This evolution occurs mainly through two processes, which explains why people can get the flu multiple times and why the vaccine must be updated annually.
The first of these processes is known as “antigenic drift.” Antigenic drift involves small, gradual mutations in the genes that code for the HA protein, which happen continually as the virus replicates. These small changes can alter the shape of the HA head, making it more difficult for existing antibodies from a past infection or vaccination to recognize and bind to it.
A more dramatic and abrupt change is called “antigenic shift.” This occurs when an influenza A virus acquires a completely new HA subtype from an animal virus. This can happen when a cell is simultaneously infected by two different flu viruses, allowing them to swap genetic material. If a new virus emerges with an HA subtype that has not circulated in humans before, most people will have no pre-existing immunity, which can lead to a pandemic.
These evolutionary changes are a challenge in creating effective long-term vaccines. Annual flu vaccines are developed based on predictions of which strains, and which specific HA proteins, will be most common during the upcoming flu season. Some research into a “universal” flu vaccine is focused on targeting the HA stalk region. Because the stalk is more conserved and changes less than the head, a vaccine that trains the immune system to attack it could offer broader protection against a wider variety of influenza strains.