Scientists have discovered that the body's rapid response in nasal cells largely determines whether a rhinovirus infection leads to a mild cold or more severe symptoms. Using lab-grown human nasal tissue, researchers showed how interferons coordinate defenses to contain the virus early. The findings, published January 19 in Cell Press Blue, emphasize the role of host responses over viral traits alone.
Rhinovirus, the leading cause of common colds, triggers an immediate defense in the nasal passages upon entry. Cells lining the nose activate antiviral mechanisms to limit the virus's spread, according to a study led by Ellen Foxman of Yale School of Medicine. This early reaction often decides if symptoms develop and their intensity, particularly in individuals with asthma or chronic lung conditions.
To investigate, the team developed organoids from human nasal stem cells, cultured for four weeks with air exposure on the upper surface. This created a multilayered tissue mimicking the nasal lining, complete with mucus-producing cells and ciliated cells that clear debris. "This model reflects the responses of the human body much more accurately than the conventional cell lines used for virology research," Foxman noted, highlighting its value for studying a human-specific virus like rhinovirus.
Experiments revealed that upon detection, infected cells release interferons—proteins that alert nearby healthy cells to bolster defenses against viral replication. A swift interferon response confines the infection, preventing symptoms. Blocking this pathway allowed the virus to proliferate, damaging tissue and even killing organoids in some cases. "Our experiments show how critical and effective a rapid interferon response is in controlling rhinovirus infection, even without any cells of the immune system present," said first author Bao Wang.
If the virus evades initial controls and replicates, it activates sensors prompting excessive mucus production and inflammation in both infected and uninfected cells. These responses contribute to airway issues and breathing difficulties. The researchers suggest targeting such pathways could yield treatments that enhance defenses while curbing harmful inflammation.
While the model lacks the full diversity of human tissues, including immune cells, it underscores that host factors are pivotal in illness outcomes. "Our study advances the paradigm that the body's responses to a virus, rather than the properties inherent to the virus itself, are hugely important in determining whether or not a virus will cause illness and how severe the illness will be," Foxman concluded. Future studies will explore additional cell interactions and environmental influences.
