The influenza virus is a highly contagious respiratory pathogen responsible for seasonal epidemics. Its success as a pathogen stems from its specialized ability to target and commandeer specific cells within the human body for its own replication. This targeted approach is how the virus establishes an infection and spreads.
The Primary Target: Respiratory Epithelial Cells
The influenza virus primarily infects the epithelial cells that line the human respiratory tract. These cells form a protective layer starting from the nose and throat in the upper respiratory system and extending down into the lungs. The specificity of the virus for these cells is due to a precise molecular interaction. The surface of respiratory epithelial cells is decorated with molecules called sialic acids, which act as receptors for the virus.
This interaction is compared to a lock and key mechanism. The “key” is a protein on the surface of the influenza virus called hemagglutinin (HA), and the “lock” is the sialic acid receptor on the host cell. When the virus is inhaled, it travels through the airways until its hemagglutinin proteins make contact with these sialic acid receptors. This binding allows the virus to attach to the cell surface and initiate the infection.
The specific chemical structure of the sialic acid receptors can vary, which influences which influenza strains can easily infect a particular species. Human influenza viruses preferentially bind to sialic acids with a specific type of molecular connection known as an alpha-2,6 linkage, which is abundant on human respiratory epithelial cells. In contrast, avian influenza viruses bind to alpha-2,3 linkages, which are more common in the intestinal tracts of birds. This difference in receptor preference is a major barrier that prevents most avian flu viruses from easily spreading among humans.
The Viral Hijacking Process
Once the virus attaches to a respiratory epithelial cell, it begins hijacking the cell’s internal machinery. The first step after attachment is entry, where the host cell is tricked into engulfing the virus particle through a process called endocytosis. Inside a cellular compartment, the virus then releases its genetic material—in the form of RNA—into the cell’s cytoplasm.
This viral RNA travels to the cell’s nucleus, the cell’s control center. Inside the nucleus, the virus uses the cell’s resources to make copies of its own genetic material and to produce messenger RNA (mRNA). This viral mRNA is then transported out of the nucleus and read by the cell’s protein-making machinery, which starts producing viral proteins, such as hemagglutinin and neuraminidase.
Newly synthesized viral RNA and proteins are then assembled into new, complete virus particles near the cell’s surface. The final step is release, where these newly formed viruses exit the host cell through a process called budding. This exit damages or destroys the host epithelial cell, allowing thousands of new virus particles to be released into the airways to infect neighboring cells.
How Infected Cells Cause Flu Symptoms
Flu symptoms are a direct consequence of both viral damage and the body’s immune response. The destruction of epithelial cells lining the respiratory tract causes localized symptoms like a sore throat, coughing, and nasal congestion, as the airway is left irritated and exposed.
Systemic symptoms, such as fever, muscle aches, and fatigue, are caused by the body’s own immune response. When the virus infects epithelial cells, these cells and responding immune cells release signaling molecules called cytokines. These cytokines act as an alarm system, recruiting other immune cells to the site of infection to fight the virus.
This flood of cytokines triggers widespread inflammation throughout the body. The resulting inflammatory state is what causes the fever, as the body attempts to create a less hospitable environment for the virus. It also leads to the muscle aches and fatigue that are characteristic of a flu infection.
Can Influenza Infect Other Cells?
While influenza is a respiratory virus, its impact is not always confined to the airways. In cases of severe infection, the virus can spread beyond the respiratory tract and infect other types of cells in the body. This phenomenon, known as extrapulmonary infection, is uncommon in seasonal flu but can occur with more aggressive strains.
Research has found evidence of the influenza virus in various non-respiratory tissues. For instance, viral components have been detected in cells of the gastrointestinal tract, which can lead to symptoms like nausea and diarrhea. In rare instances, the virus has been found in cardiac muscle cells, potentially causing inflammation of the heart, and even in cells of the central nervous system.
These occurrences are the exception. Systemic infection is associated with severe disease, where a high viral load and an intense inflammatory response may allow the virus to breach the barriers that normally contain it within the respiratory system. For the vast majority of influenza cases, the infection remains localized to the epithelial cells of the nose, throat, and lungs.