PLoS Biol 2021 Mar 17; 19(3):e3001143
There are currently limited Food and Drug Administration (FDA)-approved drugs and vaccines for the treatment or prevention of Coronavirus Disease 2019 (COVID-19). Enhanced understanding of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and pathogenesis is critical for the development of therapeutics. To provide insight into viral replication, cell tropism, and host-viral interactions of SARS-CoV-2, we performed single-cell (sc) RNA sequencing (RNA-seq) of experimentally infected human bronchial epithelial cells (HBECs) in air-liquid interface (ALI) cultures over a time course. This revealed novel polyadenylated viral transcripts and highlighted ciliated cells as a major target at the onset of infection, which we confirmed by electron and immunofluorescence microscopy. Over the course of infection, the cell tropism of SARS-CoV-2 expands to other epithelial cell types including basal and club cells. Infection induces cell-intrinsic expression of type I and type III interferons (IFNs) and interleukin (IL)-6 but not IL-1. This results in expression of interferon-stimulated genes (ISGs) in both infected and bystander cells. This provides a detailed characterization of genes, cell types, and cell state changes associated with SARS-CoV-2 infection in the human airway.
Ravindra, Neal G; Alfajaro, Mia Madel; Gasque, Victor; Huston, Nicholas C; Wan, Han; Szigeti-Buck, Klara; Yasumoto, Yuki; Greaney, Allison M; Habet, Victoria; Chow, Ryan D; Chen, Jennifer S; Wei, Jin; Filler, Renata B; Wang, Bao; Wang, Guilin; Niklason, Laura E; Montgomery, Ruth R; Eisenbarth, Stephanie C; Chen, Sidi; Williams, Adam; Iwasaki, Akiko; Horvath, Tamas L; Foxman, Ellen F; Pierce, Richard W; Pyle, Anna Marie; van Dijk, David; and Wilen, Craig B, "Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes." (2021). Faculty Research 2021. 71.