A study published in the Cell Press journal Cell Press Blue details how cells in the human nasal passages defend against rhinovirus, the primary cause of the common cold. Researchers suggest that the body's defensive response, rather than the virus itself, typically determines the onset and severity of cold symptoms.
Senior author Ellen Foxman of Yale School of Medicine highlighted the significance of rhinoviruses due to their role in common colds and respiratory issues for individuals with asthma and other chronic lung conditions. The research aimed to observe cellular and molecular activities during rhinovirus infections in the human nasal lining.
To conduct the study, scientists developed lab-grown human nasal tissue. Human nasal stem cells were cultured for four weeks and exposed to air. Under these conditions, the stem cells differentiated into a tissue containing various cell types found in human nasal passages and lung airways, including mucus-producing cells and ciliated cells.
Foxman noted that this model more accurately reflects human bodily responses compared to conventional cell lines used in virology research, especially since rhinovirus affects humans exclusively.
The model enabled the team to analyze the coordinated responses of thousands of individual cells and test how these responses changed when cellular sensors for rhinovirus were blocked. A key defensive mechanism was identified, coordinated by interferons—proteins that inhibit viral entry and replication.
Upon detecting rhinovirus, nasal lining cells produce interferons, which activate a synchronized antiviral defense in both infected and neighboring cells, creating an environment unfavorable for viral replication. If this interferon action is swift, the virus's spread can be contained. Experimental suppression of this response led to rapid viral infection of more cells, causing damage and, in some instances, organoid death.
First author Bao Wang of Yale School of Medicine stated that experiments demonstrate the critical effectiveness of a rapid interferon response in controlling rhinovirus infection, even without the presence of immune system cells.
The research also uncovered additional responses to rhinovirus that activate as viral replication increases. For example, rhinovirus can trigger another sensing system, leading to a synergistic production of excessive mucus and increased inflammation by both infected and uninfected cells. These responses can sometimes cause breathing problems in the lungs and may represent targets for interventions and the promotion of healthy antiviral responses.
The team acknowledged the organoid model's limitation in lacking certain cell types present in the body, such as immune system cells that would join the defense. Further research is planned to understand how other cell types and environmental factors in the nasal passages and airways influence the body's response to rhinovirus infection.
Foxman concluded that the study supports the paradigm that the body's response to a virus, rather than intrinsic viral properties, significantly determines illness and its severity. Targeting these defense mechanisms is considered a promising direction for new therapeutic developments.