Every time you sneeze or cough during an infection, you may be doing exactly what the virus wants. While the immune system clears most infections, viruses have evolved ways to escape the respiratory tract and reach new hosts. They achieve this by altering airway neuronal control, enhancing reflexes that expel virus-laden droplets, and stimulating parasympathetic mucus secretion. Reflexes the body evolved for protection have been co-opted as tools of spread.

Distinct Neural Pathways: Why Sneezing and Coughing Are Different

For a long time, scientists assumed that coughing and sneezing were controlled by the same neural circuits, since both are reflexes designed to clear the respiratory tract. Recent research, however, has revealed that these two reflexes are actually controlled by separate populations of sensory nerves.

Sneezing is triggered by a specific set of neurons in the nasal passages called MrgprC11⁺MrgprA3⁻ neurons. These cells detect irritants like dust, pollen, or viral particles in the nose. When activated, they send signals to the brain, which responds by initiating a powerful sneezing reflex, expelling droplets and mucus from the upper airways. Coughing, in contrast, is controlled by a different set of neurons, known as somatostatin-expressing (SST⁺) neurons, located primarily in the trachea and lower airways. These neurons detect irritation deeper in the respiratory system and trigger the cough reflex to clear the lungs and bronchi.

This separation is important because viruses can exploit it to their advantage. By infecting different parts of the respiratory tract, a virus can selectively trigger sneezing or coughing depending on its preferred site of replication. A virus in the nose can induce sneezing to spread through airborne droplets, while a virus in the lower lungs can stimulate coughing to expel particles more effectively from the chest.

Viral Activation of Neural Reflexes

The mechanism is indirect: infected cells release chemical signals that trigger the very reflexes viruses depend on for spread. When viruses infect airway epithelial cells, these infected cells release inflammatory mediators and chemical alarm signals. These molecules activate sensory nerve endings located just beneath the airway surface, which are equipped with specialized receptors that detect signs of infection or tissue damage.

Once activated, these sensory neurons send signals along specific neural pathways to respiratory control centers in the brainstem. The brain’s response depends on which sensory nerves were triggered.

When nasal infection occurs, it activates trigeminal sensory neurons that project to “sneeze control centres”, triggering the sneeze reflex to expel material from the upper airways. In contrast, when lower airway infection develops, it activates vagal sensory neurons innervating the trachea and bronchi, which project to “cough control centres” and initiate the cough reflex to clear the lower respiratory tract.

These changes are not always temporary. Viruses can cause lasting alterations in the nerves themselves, a phenomenon called neuroplasticity. After an infection, sensory nerves in the airways can become more sensitive, making a person prone to coughing in response to even mild irritants. The virus, in effect, leaves a signature in the nervous system that persists well beyond the acute infection.

The Parasympathetic Nervous System: The Mucus Factory

Viruses also manipulate the parasympathetic nervous system, a branch of the autonomic nervous system that controls involuntary bodily functions, including mucus secretion. Viral infection can alter nerve cell activity in the vagal ganglia, clusters of nerve cells that communicate with the lungs and airways, resulting in stronger signals that stimulate mucus-producing glands.

This has two effects. First, it produces more mucus, which carries viral particles and keeps them viable outside the host. Second, it ensures that the mucus is ready to be expelled during sneezing or coughing, creating an efficient delivery system for the virus to reach new hosts. In other words, the virus turns your own mucus and reflexes into tools for its spread.

Evolutionary Perspective

This neural hijacking is the product of millions of years of viral evolution. By manipulating host reflexes, viruses enhance transmission while avoiding immediate immune detection. It is a reminder that in the relationship between virus and host, the line between symptom and strategy is rarely as clear as it seems.

How VRS Can Help

Understanding how viruses interact with airway epithelium is central to developing better antivirals and infection models. At VRS, we offer Air-Liquid Interface (ALI) cell culture services using primary human bronchial epithelial cells; one of the most physiologically relevant systems for studying respiratory virus behaviour. If you’re working on a respiratory virus project, get in touch to discuss how we can support your research.