When the rhinovirus, which is the most frequent cause of the common cold, attacks the lining of the nasal passages, our cells mobilize, initiating a complete arsenal of antiviral countermeasures. In a paper published in the journal Cell Press Blue, researchers illustrate how cells within the nose cooperate to shield us from the cold. The scientists propose that the body’s defense against the rhinovirus, rather than the virus itself, typically dictates whether we become ill and how severe our symptoms will be.
“Rhinoviruses are the primary cause of the common cold and respiratory problems in people with asthma and other chronic lung diseases,” states Ellen Foxman, the study’s senior author from the Yale School of Medicine. “This investigation allowed us to examine the human nasal lining and grasp what happens at both the cellular and molecular levels during a rhinovirus infection.”
To accomplish this, the scientists grew human nasal tissue in a laboratory setting. They cultured human nasal tissue stem cells for four weeks, exposing them to air. Under these conditions, the stem cells matured into tissue containing numerous cell types found in human nasal passages and lung airways, including mucus-producing cells and ciliated cells—mobile, hair-like structures that push mucus out of the lungs.
“This model more accurately represents human body reactions than the typical cell lines employed in virology studies,” Foxman notes. “Since the rhinovirus only causes disease in humans and not other animals, human tissue organoid models are especially valuable for studying this virus.”
The model made it possible to examine the synchronized responses of thousands of individual cells simultaneously and to test how these responses change when the cellular sensors that detect the rhinovirus are blocked. In observing this, the researchers witnessed a defensive mechanism that restrains rhinovirus infections and is coordinated by interferons—proteins that prevent viruses from entering and replicating.
Upon detecting the rhinovirus, the cells of the nasal lining release interferons, which trigger a coordinated antiviral defense in both the infected cells and their neighbors, rendering the environment unsuitable for viral replication. If interferons are deployed quickly enough, the virus cannot spread. When the researchers experimentally prevented this response, the virus rapidly infected a much larger number of cells, leading to damage and, in some cases, the death of the infected organoids.
“Our experiments demonstrate the critical importance and efficacy of a rapid interferon response in combating rhinovirus infection, even in the absence of immune system cells,” says Bao Wang, the study’s first author.
The research also uncovered other reactions to the rhinovirus that manifest when viral replication intensifies. For instance, the rhinovirus can activate a different sensory system that prompts infected and uninfected cells to synergistically produce excessive mucus, heighten inflammation, and occasionally cause respiratory issues in the lungs. According to the researchers, these reactions could serve as good targets for interventions aimed at combating rhinovirus infection and promoting a healthy antiviral response.
The team acknowledges that the organoids used contain a limited range of cell types compared to what is present in the body; in a living organism, infection recruits other cells, including those from the immune system, to defend against the rhinovirus. The subsequent step in their work will involve exploring how other cell types and environmental factors within the nasal passages and airways influence the body’s response to the infection.
“The study enhances the understanding that the body’s reaction to a virus, rather than the properties of the virus itself, plays the key role in determining whether the virus will cause illness and how severe it will be,” Foxman concludes. “Targeting these defense mechanisms presents a promising avenue for developing new treatments.” Information sourced from the portal “Scientific Russia” (https://scientificrussia.ru/)
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