Researchers found that during a rhinovirus infection, rapid production of interferons can ward off imminent danger. Without this response, the infection quickly spreads to cells.
As temperatures drop, flu season begins to surge, bringing with it the familiar symptoms of respiratory illness. People may cycle through boxes of tissues, turn to hot beverages for relief, or attempt to sleep off their sickness.
Among the viruses responsible for these seasonal illnesses, rhinovirus (RV) is one of the most frequent causes of the common cold and can trigger more severe respiratory distress in smokers and individuals with asthma. Despite its prevalence, the molecular mechanisms that drive such varied outcomes among infected individuals remain poorly understood.
This motivated immunobiologist Ellen Foxman from Yale School of Medicine to investigate nasal cell responses to RV infection with the goal of identifying the molecular processes that influence susceptibility to viral disease. Her team’s findings, published in Cell Press Blue, revealed that nasal tissue organoids produced interferons (IFNs) to stave off RV infection, but if this response was too slow, the virus quickly infected and damaged cells.1 These findings underscore the importance of an effective and rapid IFN response even without immune cells present.
Since a key antiviral defense of respiratory epithelial cells is the IFN response, Foxman and her team homed in on its activity during RV infection. To study this, researchers generated human nasal cell organoids, which included mucosal epithelial cell types that produce mucus and ciliated cells. “This model reflects the responses of the human body much more accurately than the conventional cell lines used for virology research,” explained Foxman in a statement.
The team found that RV infection induced the epithelial cells to increase IFN activity and limit viral replication. This response did not occur when the researchers treated the cells with an IFN inhibitor; instead, they observed increased viral load and cell death.
Using single-cell RNA sequencing (scRNA-seq), the researchers found that inhibiting IFN induction also resulted in a higher percentage of infected cells, particularly ciliated cells. In addition, other responses kicked in that can contribute to breathing problems, such as mucus hyperproduction in infected and uninfected cells, and increased inflammation. These responses may be promising targets in treating RV infections.
The team observed increased expression of interferon-specific genes in the first two days of infection, which later tapered off. Meanwhile, other transcriptional programs likely related to the resolution of the antiviral response increased. These patterns also paralleled human scRNA-seq data from adults with and without SARS-CoV-2 infection.
“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. While the organoid model only accounts for a limited number of cell types, the findings underscore distinct host responses. Foxman added that, “Targeting defense mechanisms is an exciting avenue for novel therapeutics.”
