Influenza viruses are common respiratory pathogens that cause seasonal epidemics and occasional pandemics. Like all viruses, influenza must enter a host cell to replicate and produce new viral particles. The first step in this infection process involves the virus attaching to specific molecules on the surface of a host cell. This initial binding event determines which cells the virus can infect and is a foundational step for the spread of influenza within the body.
The Primary Target Cells
Influenza viruses primarily target epithelial cells that line the respiratory tract. These cells are found in the nose, throat, and lungs, forming the protective barrier of the airways.
When influenza infects these cells, it can lead to symptoms such as fever, cough, sore throat, and body aches. Infection of these cells allows the virus to replicate efficiently and spread throughout the respiratory system. While epithelial cells are the main targets, some immune cells like macrophages and dendritic cells can also be susceptible to infection.
How Influenza Binds to Cells
Influenza initiates infection by using a protein on its surface called hemagglutinin (HA). Hemagglutinin acts like a “key” that recognizes and binds to specific “locks” on the surface of host cells. These “locks” are carbohydrate molecules called sialic acids, which are found on glycoproteins and glycolipids of the cell membrane.
The binding process involves multiple HA molecules on the viral envelope attaching to multiple sialic acid receptors on the host cell surface. This interaction is highly specific, with different influenza strains having variations in their HA protein that influence which sialic acid structures they prefer to bind.
What Happens After Binding
Once influenza successfully binds to the sialic acid receptors on the host cell surface, the cell begins to engulf the virus through a process called endocytosis. The virus is enclosed within a vesicle, called an endosome, which is then pulled inside the cell.
As the endosome travels deeper into the cell, its internal environment becomes more acidic. This drop in pH triggers a change in the shape of the viral hemagglutinin protein, allowing the viral envelope to fuse with the endosomal membrane. This fusion event leads to the release of the viral genetic material, specifically the viral ribonucleoproteins (vRNPs), into the cell’s cytoplasm. The vRNPs then travel to the cell’s nucleus, where viral replication begins.
Why Influenza Targets Specific Cells
The specificity of influenza virus targeting is determined by viral tropism, dictated by the type of sialic acid receptors present on different cell types. Sialic acids can be linked to other sugars in different configurations, primarily alpha 2,6-linked or alpha 2,3-linked, which determines which cells an influenza virus can bind.
Human influenza viruses predominantly bind to alpha 2,6-linked sialic acids, abundant in the epithelial cells of the human upper respiratory tract. In contrast, avian influenza viruses prefer alpha 2,3-linked sialic acids, more common in the lower respiratory tract of humans or in the gut of birds. This difference in receptor preference explains why avian influenza strains have limited human-to-human transmission, as the primary receptors they favor are less prevalent in the human upper respiratory tract.