Rhinoviruses are the most frequent cause of common colds. When these viruses infect cells lining the nasal passages, the cells there usually work together to fight them and prevent symptoms.

In high-risk groups such as smokers and people with asthma, however, a rhinovirus infection can cause serious illness.

Unfortunately, the mechanisms behind these very strong responses to rhinoviruses have been poorly understood.

Proteins trigger an interferon-coordinated response between infected cells and neighboring cells that blocks the virus's ability to replicate.

Researchers at Yale University were recently able to demonstrate how the cells in human nasal passages work together to prevent rhinovirus infection. Their findings suggest it is the body's defense mechanisms, rather than rhinoviruses themselves, that determine whether people will catch a cold or not and how bad the symptoms will be.

The researchers created models of nasal tissue. They grew stem cells from human nasal passages in the lab for four weeks and exposed the top layer of these cells to air. The cells grew, or differentiated, into the different types of cells found in human nasal passages.

The lab-grown cells were able to mimic the important features of human diseases better than the typical cell lines used in virology research, Ellen Foxman, senior author on the study, explained. She was surprised at how much researchers can learn from these models, called organoids.

Rhinoviruses cause illness in humans but do not affect other animals, making lab-grown models of human tissues particularly valuable for studying them.

“This research allowed us to peer into the human nasal lining and see what is happening during rhinovirus infections at both the cellular and molecular levels,” Foxman, an associate professor of laboratory medicine and immunobiology at Yale School of Medicine, told TheDoctor.

The models also allowed researchers to examine the responses of thousands of these cells.

When cells in the nasal lining detect a rhinovirus, they produce proteins called interferons. These proteins trigger a coordinated response between infected cells and neighboring cells that blocks the virus's ability to replicate.

The rhinovirus cannot spread if less than two percent of cells become infected. But when the researchers prevented this interferon-coordinated response, the virus spread quickly and was able to infect more than 30 percent of the model cells, even killing the infected organoids in some cases.

It is likely that the body's defense mechanisms, rather than rhinoviruses themselves, determine if people catch a cold or not and how bad the symptoms will be.

“These experiments show how important and effective a rapid interferon response is for controlling rhinovirus infection,” Bao Wang, first author on the study and a member of Foxman's lab at Yale, said in a statement.

The stem cells in the models also differentiated into cells lining the airways in the lungs, including cells that produce mucus and those with cilia, the hair-like structures that sweep mucus out of the lungs.

An increase in rhinovirus replication triggered other responses as well. As everyone who has had a cold knows, viral replication triggers infected and uninfected cells to become inflamed and produce excessive amounts of mucus that make it hard to breathe.

“We now know these particular pathways are the most important for fighting this particular virus,” said Foxman. “Now we can figure out why people with certain risk factors, such as asthma or tobacco use, have the wrong reaction to the virus.”

The study is published in Cell Press Blue.