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SARS-CoV-2 Entry Genes Are Most Highly Expressed in Nasal Goblet and\nCiliated Cells within Human Airways

Year: 2020
Type: article
Abstract: The SARS-CoV-2 coronavirus, the etiologic agent responsible for COVID-19\ncoronavirus disease, is a global threat. To better understand viral tropism, we\nassessed the RNA expression of the coronavirus receptor, ACE2,\nas well as the viral S protein priming protease TMPRSS2 thought\nto govern viral entry in single-cell RNA-sequencing (scRNA-seq) datasets from\nhealthy individuals generated by the Human Cell Atlas consortium. We found that\nACE2, as well as the protease TMPRSS2, are\ndifferentially expressed in respiratory and gut epithelial cells. In-depth\nanalysis of epithelial cells in the respiratory tree reveals that nasal\nepithelial cells, specifically goblet/secretory cells and ciliated cells,\ndisplay the highest ACE2 expression of all the epithelial cells\nanalyzed. The skewed expression of viral receptors/entry-associated proteins\ntowards the upper airway may be correlated with enhanced transmissivity.\nFinally, we showed that many of the top genes associated with\nACE2 airway epithelial expression are innate\nimmune-associated, antiviral genes, highly enriched in the nasal epithelial\ncells. This association with immune pathways might have clinical implications\nfor the course of infection and viral pathology, and highlights the specific\nsignificance of nasal epithelia in viral infection. Our findings underscore the\nimportance of the availability of the Human Cell Atlas as a reference dataset.\nIn this instance, analysis of the compendium of data points to a particularly\nrelevant role for nasal goblet and ciliated cells as early viral targets and\npotential reservoirs of SARS-CoV-2 infection. This, in turn, serves as a\nbiological framework for dissecting viral transmission and developing clinical\nstrategies for prevention and therapy.
Language: English
Field: Medicine
Open Access status: green
OpenAlex ID: W7071329396
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