When a rhinovirus infects the nasal passages, the body’s response is crucial in determining whether an individual develops symptoms and how severe those symptoms become, according to new research published January 19 in Cell Press Blue. The study was conducted using lab-grown human nasal tissue that closely mimics the environment of actual human airways.
Researchers cultivated human nasal stem cells for four weeks, exposing them to air so they would develop into tissues similar to those found in the nose and lungs. These tissues included mucus-producing cells and ciliated cells, which help clear mucus from the respiratory tract.
"This model reflects the responses of the human body much more accurately than the conventional cell lines used for virology research," said Foxman. "Since rhinovirus causes illness in humans but not other animals, organotypic models of human tissues are particularly valuable for studying this virus."
The study focused on how these cells coordinate their defenses against rhinovirus infection. The researchers found that when cells detect rhinovirus, they produce interferons—proteins that trigger antiviral activity both within infected cells and their neighbors. This rapid interferon response can prevent viral spread if it occurs quickly enough.
"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 of Yale School of Medicine.
If this defense mechanism is blocked or delayed, researchers observed that rhinovirus spreads more easily among cells, causing greater damage to tissue samples. In addition to interferon-driven responses, increased viral replication also activated other pathways—such as excessive mucus production and inflammation—that can lead to breathing difficulties.
The team noted that while their laboratory model captures key aspects of nasal defense, it lacks some cell types present in living organisms—particularly immune system cells recruited during infection. They highlighted future research directions aimed at understanding how these additional cell types and environmental factors influence antiviral responses.
"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 said. "Targeting defense mechanisms is an exciting avenue for novel therapeutics."
Funding for this research came from several sources including the Yale Colton Center for Autoimmunity, Rita Allen Foundation, and China Scholarship Council Yale World Scholars Fellowship.
