Where the common cold is stopped before it starts
By Cell Press
When rhinovirus, the leading cause of the common cold,
infects the lining of the nose, cells in the nasal passages immediately begin
working together to defend against it. These cells activate a broad range of
antiviral responses designed to limit infection. In a study published today
(January 19) in the Cell Press journal Cell Press Blue, researchers
show that this coordinated cellular defense plays a major role in whether a
person gets sick at all and how severe their symptoms become. The findings
suggest that the body’s reaction to rhinovirus, rather than the virus alone, is
often what determines the outcome of infection.
“As the number one cause of common colds and a major cause
of breathing problems in people with asthma and other chronic lung conditions,
rhinoviruses are very important in human health,” says senior author Ellen
Foxman of Yale School of Medicine. “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.”
Building a Human Model of the Nasal Lining
To closely study these early defenses, the research team
grew human nasal tissue in the lab. They cultured nasal stem cells for four
weeks while exposing the upper surface to air. This process encouraged the
cells to develop into a complex tissue that closely resembles the lining of
human nasal passages and lung airways. The resulting tissue included
mucus-producing cells as well as cells with cilia, which are tiny hair-like
structures that help move mucus out of the lungs.
“This model reflects the responses of the human body much
more accurately than the conventional cell lines used for virology research,”
Foxman says. “Since rhinovirus causes illness in humans but not other animals,
organotypic models of human tissues are particularly valuable for studying this
virus.”
Interferons and Early Antiviral Defense
Using this lab-grown tissue, the scientists were able to
observe how thousands of individual cells respond at the same time. They also
tested what happens when the cellular sensors that recognize rhinovirus are
blocked. These experiments revealed a powerful protective system driven by
interferons, which are proteins that prevent viruses from entering cells and
making copies of themselves.
When nasal cells detect rhinovirus, they release interferons
that activate antiviral defenses both in infected cells and in nearby healthy
cells. This coordinated response creates an environment that is hostile to
viral spread. If interferon activity begins quickly, the virus is often stopped
before it can spread further. When researchers experimentally shut down this
response, rhinovirus spread rapidly through the tissue, damaging cells and, in
some cases, killing the infected organoids.
“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,” says first author Bao Wang of Yale School
of Medicine.
When the Defense Response Goes Too Far
The study also identified additional responses that emerge
when viral replication increases. In these situations, rhinovirus can activate
a separate sensing pathway that leads both infected and uninfected cells to
collectively produce large amounts of mucus and inflammatory signals. This
reaction can contribute to airway inflammation and, in some cases, breathing
difficulties. According to the researchers, these pathways may offer promising
targets for treatments that reduce harmful symptoms while preserving protective
antiviral responses.
Limits of the Model and Next Steps
The researchers note that their organoid system does not
include all the cell types found in the human body. During real infections,
additional cells, including immune cells, are drawn to the site to help fight
the virus. Understanding how these cells and other environmental factors in the
nasal passages and airways influence the body’s response to rhinovirus will be
an important focus of future studies.
“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 says. “Targeting defense mechanisms is an
exciting avenue for novel therapeutics.”
Reference: “Rhinovirus triggers distinct host responses
through differential engagement of epithelial innate immune signaling” 19
January 2026, Cell Press Blue.
DOI: 10.1016/j.ccell.2025.11.008
This study was supported by funding from the Yale Colton
Center for Autoimmunity, the Rita Allen Foundation, and the China Scholarship
Council Yale World Scholars Fellowship.
