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  • Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes #MMPMID33730024
  • Ravindra NG; Alfajaro MM; Gasque V; Huston NC; Wan H; Szigeti-Buck K; Yasumoto Y; Greaney AM; Habet V; Chow RD; Chen JS; Wei J; Filler RB; Wang B; Wang G; Niklason LE; Montgomery RR; Eisenbarth SC; Chen S; Williams A; Iwasaki A; Horvath TL; Foxman EF; Pierce RW; Pyle AM; van Dijk D; Wilen CB
  • PLoS Biol 2021[Mar]; 19 (3): e3001143 PMID33730024show ga
  • 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.
  • |*Gene Expression[MESH]
  • |Adult[MESH]
  • |Bronchi/*pathology/virology[MESH]
  • |COVID-19/*diagnosis/immunology/pathology/virology[MESH]
  • |Cells, Cultured[MESH]
  • |Epithelium/pathology/virology[MESH]
  • |Humans[MESH]
  • |Immunity, Innate[MESH]
  • |Longitudinal Studies[MESH]
  • |SARS-CoV-2/genetics/*isolation & purification[MESH]
  • |Single-Cell Analysis/*methods[MESH]
  • |Transcriptome[MESH]
  • |Viral Tropism[MESH]

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  • suck abstract from ncbi

    e3001143 3.19 2021