Influenza viruses possess unique surface proteins fundamental to their ability to infect and spread. Hemagglutinin (HA) and neuraminidase (NA) are found on the virus’s outer envelope and play roles in the viral life cycle. Understanding these proteins is central to comprehending how the flu virus operates and how our bodies and medical interventions combat it.
Hemagglutinin’s Role in Infection
Hemagglutinin acts as the virus’s “key” for gaining entry into host cells. This glycoprotein is a trimer, composed of three identical subunits. Each HA subunit contains a receptor binding site that binds to sialic acid residues found on the surface of host cells, particularly those lining the respiratory tract. This initial binding step allows the virus to adhere to a cell.
Following attachment, the host cell engulfs the virus through endocytosis, creating a membrane-bound compartment called an endosome. As the endosome acidifies, the lower pH triggers a change in the HA protein’s shape. This conformational shift exposes a “fusion peptide” that inserts into the endosomal membrane, pulling the viral and host membranes together and causing them to fuse. This fusion releases the viral genetic material into the host cell’s cytoplasm, allowing the infection to proceed.
Neuraminidase’s Role in Release
Neuraminidase, in contrast to hemagglutinin, functions as the virus’s “exit strategy” from infected cells. This enzyme is also a glycoprotein. After the virus replicates inside a host cell and new viral particles form, they bud off from the cell’s plasma membrane.
Newly formed virions can remain attached to the host cell surface due to the continued binding of their hemagglutinin to sialic acid receptors. Neuraminidase cleaves these sialic acid molecules from both the host cell surface and from the surface of newly budded viral particles. This enzymatic action prevents new viruses from clumping together or re-attaching to the infected cell, facilitating their release and spread to new, uninfected cells.
Understanding Flu Strain Names
The specific types of hemagglutinin (H) and neuraminidase (N) proteins classify and name influenza A virus strains. There are 18 known HA subtypes (H1-H18) and 11 known NA subtypes (N1-N11), though only a few circulate widely in humans, such as H1, H2, H3, N1, and N2. This classification system gives rise to names like H1N1 or H3N2, where numbers denote the specific HA and NA subtypes present on the virus’s surface.
Influenza viruses constantly change through two main processes: antigenic drift and antigenic shift. Antigenic drift involves small, gradual mutations in the genes encoding HA and NA proteins during viral replication. These minor changes accumulate over time, leading to new variants that the human immune system may not fully recognize from previous infections or vaccinations. This continuous drift is why new flu vaccines are needed annually.
Antigenic shift is an abrupt, major change that can occur when two different influenza A viruses infect the same host cell. This co-infection allows for the exchange of entire gene segments between the viruses, a process called reassortment. If a novel HA or NA protein, or a new combination, emerges from this reassortment, it can result in a new subtype to which the human population has little or no existing immunity, potentially leading to pandemics.
Developing Flu Vaccines and Treatments
Understanding HA and NA is fundamental to developing effective strategies against influenza. Flu vaccines primarily work by targeting hemagglutinin. The vaccine introduces HA proteins from predicted circulating strains, prompting the immune system to produce antibodies that bind to these proteins. These HA-specific antibodies then block the virus from attaching to and entering host cells, preventing infection.
While current vaccines focus on HA, research explores targeting neuraminidase for broader protection. Antiviral drugs, known as neuraminidase inhibitors, specifically target the NA enzyme. Medications like oseltamivir (Tamiflu) and zanamivir (Relenza) work by binding to neuraminidase, preventing it from cleaving sialic acid. This inhibition traps newly replicated viruses on the surface of the infected cell, preventing their release and subsequent spread to other cells in the body.