부산대학교 도서관

The human airway epithelium is the initial site of SARS-CoV-2 infection. We used flow cytometry and single cell RNA-sequencing to understand how the heterogeneity of this diverse cell population contributes to elements of viral tropism and pathogenesis, antiviral immunity, and treatment response to remdesivir. We found that, while a variety of epithelial cell types are susceptible to infection, ciliated cells are the predominant cell target of SARS-CoV-2. The host protease TMPRSS2 was required for infection of these cells. Importantly, remdesivir treatment effectively inhibited viral replication across cell types, and blunted hyperinflammatory responses. Induction of interferon responses within infected cells was rare and there was significant heterogeneity in the antiviral gene signatures, varying with the burden of infection in each cell. We also found that heavily infected secretory cells expressed abundant IL-6, a potential mediator of COVID-19 pathogenesis. Author summary: SARS-CoV-2 infects the respiratory tract, targeting cells of the diverse airway epithelium. Infection outcomes depend on several factors that may vary in this heterogenous population including viral tropism, antiviral immunity, and response to antiviral therapies like remdesivir. We found that SARS-CoV-2 infects an array of airway epithelial cells, relying on the host protease TMPRSS2 for entry. Ciliated epithelial cells were the dominant target, and remdesivir blocked viral replication across multiple cell types. We uncovered cellular heterogeneity in early antiviral immunity to SARS-CoV-2 and identified cell type-specific ISGs associated with either high levels of viral replication or protection from infection. [ABSTRACT FROM AUTHOR]