The nasal passages defend humans against the common cold and help determine the severity of the disease, according to research that looked at the lining of this facial organ and saw what happens during rhinovirus infections at both the cellular and molecular levels.
Behind the study are scientists from Yale University School of Medicine, USA, who created lab-grown human nasal tissue for their analysis. The findings reinforce the theory that the body’s responses to a virus, rather than the inherent properties of the virus itself, are hugely important in determining whether it will cause disease and the severity. Details are published Monday in the scientific journal Cell Press Blue.
When a rhinovirus, the most common cause of the common cold, infects the lining of the nasal passages, cells work together to fight the virus by activating an arsenal of antiviral defenses.
To demonstrate how they do this and to scrutinize the nasal lining, the team led by Ellen Foxman created lab-grown human nasal tissue.
They cultured human nasal stem cells for four weeks while exposing the upper surface to air.
Under these conditions, the stem cells differentiated into a tissue with many of the cell types found in human nasal passages and lung airway linings, including mucus-producing cells and those with cilia, hair-like structures that sweep mucus from the lungs.
“This model reflects the responses of the human body much more accurately than conventional cell lines used for virology research,” Foxman says in a statement.
“Since rhinovirus causes disease in humans, but not in other animals, organotypic models of human tissues are especially valuable for studying this virus.”
The model allowed the team to examine the coordinated responses of thousands of individual cells at a time and to test how the reactions changed when cellular sensors that detect rhinovirus were blocked.
In doing so, the researchers observed a defensive mechanism that keeps rhinovirus infections at bay, coordinated by interferons, proteins that block virus entry and replication.
Upon detection of rhinovirus, cells in the nasal lining produce interferons, which induce a coordinated antiviral defense of infected and neighboring cells, making the environment inhospitable to viral replication.
If the interferons act fast enough, the virus cannot spread.
When the researchers experimentally prevented this response, the virus rapidly infected many more cells, causing damage and, in some cases, death of the infected organoids.
The research, which is in line with other studies, also revealed other responses to rhinovirus that are activated when viral replication increases.
For example, rhinovirus can trigger a different detection system that causes infected and uninfected cells to synergistically produce excess mucus, increase inflammation and sometimes cause respiratory problems in the lungs.
These responses may be good targets for intervening in rhinovirus infection and promoting a healthy antiviral response, conclude the researchers, who acknowledge, however, that the organoids used contain limited cell types compared to those in the human body, so further research is needed.
“Focusing on defense mechanisms is an exciting avenue for developing new therapies,” stresses Foxman, who defends the importance of these results.
With information from EFE
