Coronavirus in vitro
Respiratory tract model infected with covid
Tatiana Matveeva, "Scientific Russia"
The model can be used to test potential drugs, the press service of the Boston Children's Hospital (USA) reports. The results of the study are published in the American Journal of Physiology — Lung Cellular and Molecular Physiology (Wang et al., Human airway lineage derived from pluripotent stem cells reveal the epithelial responses to SARS-CoV-2 infection).
To build the model, the researchers took blood cells from two people and genetically "reprogrammed" them back into the stem cell state. They then forced the stem cells to form all the major types of epithelial cells lining the trachea and bronchi, including ciliated, secretory, and basal cells. The key cellular receptor ACE2 was also reproduced, as was TMPRSS2, the main enzyme that promotes the penetration of the virus.
After the scientists infected the model with a live SARS-CoV-2 virus and showed that the cells of the respiratory tract with many cilia are the starting point of the virus penetration. "This is important because ciliated cells perform an important function in moving the mucus of the respiratory tract and trapped pathogens from the lungs," the authors of the work note. "If the ciliated cells are damaged, it is easier for the virus to get into the lower parts of the lungs."
Three ciliated cells in this model are infected with a virus.
After infection, the respiratory tract model showed a sustained antiviral response by conducting type 1 and type 3 interferons. The team also observed a noticeable inflammatory response with increased production of inflammatory signaling molecules and increased expression of interferon-stimulated genes and genes involved in the activation of immune cells.
Since the respiratory tract model genetically corresponds to the patient from whom the cells were obtained, it allows us to check how COVID-19 affects patients with specific concomitant diseases.
The team also tested the antiviral drug remdesivir on the model and found that the virus spreads less under the influence of the drug. The scientists saw the same thing when they tested camostat mesylate, which inhibits TMPRSS2, confirming that the virus requires TMPRSS2 to infect respiratory tract cells.
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