There are more than [number] known to science. These common cold-causing viruses are found [location], and while rhinovirus infections typically result in copious mucus and discomfort, they often produce no symptoms whatsoever.
However, while rhinoviruses are generally harmless to most individuals, infection can be life-threatening for others.
Over the past few decades, research has shown that rhinovirus infections are [significant], and for those with chronic obstructive pulmonary disease (COPD), they are a primary trigger of exacerbations, leading to shortness of breath and coughing that can turn dangerous if not treated.
The variation in symptom severity does not appear to stem from the virus itself. “It’s now quite evident that if you infect someone with asthma or COPD with a rhinovirus and then infect a healthy individual with the same dose of rhinovirus, the responses are notably distinct,” says Aran Singanayagam, a clinician scientist at Imperial College London who studies respiratory disease.
To gain deeper insight into this phenomenon, scientists have utilized lab-grown nasal tissue infected with rhinovirus. Now, in a study published in the journal Cell Press Blue, researchers report that if the tissue’s initial defenses falter, what might have been a mild infection escalates into a severe one. This finding, supported by single-cell data, confirms that disparities in the host’s immune system—not the virus’s behavior—are responsible for these outcomes.
A detrimental delay
When lab-grown nasal tissue “catches a cold,” only a small number of cells are actually infected with the virus, says Ellen Foxman, a professor of immunobiology at Yale School of Medicine and an author of the new paper. “We observe something quite analogous to what is often seen in individuals with a mild or asymptomatic cold,” she notes. “Just around 1% of the cells become infected.”
Nonetheless, all cells in the tissue exhibited altered behavior. Molecules released by the infected cells—called interferons—served as warning signals to neighboring cells, prompting them to activate their antiviral defenses. Consequently, the virus was unable to spread beyond the initially infected cells.
What would occur if that interferon signal failed to transmit? Foxman and her team wondered. They used a drug to block the warning and observed a starkly different outcome. Before their eyes, the tissue began to secrete mucus, and the cells started producing signals intended to trigger inflammation. “This is what we observe in individuals with a cold or those experiencing asthma or COPD attacks—excessive mucus production and the recruitment of inflammatory cells to the lungs,” Foxman says.
“Timing is crucial,” she adds. “If the response is delayed sufficiently to allow the virus to replicate and grow large enough to activate other pathways, that’s when symptoms will manifest.”
This delay aligns with [previous findings], says Nathan Bartlett, a professor at University of Newcastle in Australia and Hunter Medical Research Institute who studies rhinovirus. “We discovered that if you take cells from an airway chronically exposed to inflammation, they become desensitized,” he explains. “They simply take a bit longer to detect an infection. As a result, we observed a delay of approximately 24 hours.”
For a rhinovirus, this is significant—a 24-hour delay allows the virus to multiply exponentially before neighboring cells receive the warning. By the time cells finally respond, there is a far greater viral load to combat, leading to more severe damage.
A way forward
Notably, this new study focused on a specific subset of nasal cells—the lab-grown tissue lacked specialized immune cells, such as those that would be recruited in a natural human nasal response to a virus. However, the study identifies the signals cells emit when their first-line defenses are compromised, which Foxman hopes will aid in identifying drug targets to prevent severe reactions to rhinovirus.
However, the window for intervening in the unchecked inflammatory process that begins when normal signaling fails is very narrow. It might make the most sense, speculates Bartlett, to consider a more universal treatment or even, perhaps, a vaccine that could protect vulnerable individuals before complications develop.
“I’ve recently encountered several papers discussing universal [vaccines/treatments],” he says, which could potentially boost the immune system to defend against various viruses. If such a vaccine is ever clinically available, scientists will closely monitor its impact on rhinovirus infections.
“We can now include rhinovirus in these discussions,” he says, “because that’s probably the virus we’ll encounter most frequently. Therefore, we need to start prioritizing it.”
