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10.1101/2020.05.06.081695

http://scihub22266oqcxt.onion/10.1101/2020.05.06.081695
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32511382!7263511!32511382
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suck abstract from ncbi


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pmid32511382      bioRxiv 2020 ; ä (ä): ä
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  • Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium #MMPMID32511382
  • Ravindra NG; Alfajaro MM; Gasque V; Habet V; Wei J; Filler RB; Huston NC; Wan H; Szigeti-Buck K; Wang B; Wang G; Montgomery RR; Eisenbarth SC; Williams A; Pyle AM; Iwasaki A; Horvath TL; Foxman EF; Pierce RW; van Dijk D; Wilen CB
  • bioRxiv 2020[Jul]; ä (ä): ä PMID32511382show ga
  • SARS-CoV-2, the causative agent of COVID-19, has tragically burdened individuals and institutions around the world. There are currently no approved drugs or vaccines for the treatment or prevention of COVID-19. Enhanced understanding of SARS-CoV-2 infection and pathogenesis is critical for the development of therapeutics. To reveal insight into viral replication, cell tropism, and host-viral interactions of SARS-CoV-2 we performed single-cell RNA sequencing of experimentally infected human bronchial epithelial cells (HBECs) in air-liquid interface cultures over a time-course. This revealed novel polyadenylated viral transcripts and highlighted ciliated cells as a major target of infection, which we confirmed by electron microscopy. Over the course of infection, 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 IFNs and IL6 but not IL1. This results in expression of interferon-stimulated genes in both infected and bystander cells. We observe similar gene expression changes from a COVID-19 patient ex vivo. In addition, we developed a new computational method termed CONditional DENSity Embedding (CONDENSE) to characterize and compare temporal gene dynamics in response to infection, which revealed genes relating to endothelin, angio-genesis, interferon, and inflammation-causing signaling pathways. In this study, we conducted an in-depth analysis of SARS-CoV-2 infection in HBECs and a COVID-19 patient and revealed genes, cell types, and cell state changes associated with infection.
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