RT Journal Article
SR Electronic
T1 Single cell resolution of SARS-CoV-2 tropism, antiviral responses, and susceptibility to therapies in primary human airway epithelium
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.19.343954
DO 10.1101/2020.10.19.343954
A1 Jessica K. Fiege
A1 Joshua M. Thiede
A1 Hezkiel Nanda
A1 William E. Matchett
A1 Patrick J. Moore
A1 Noe Rico Montanari
A1 Beth K. Thielen
A1 Jerry Daniel
A1 Emma Stanley
A1 Ryan C. Hunter
A1 Vineet D. Menachery
A1 Steven S. Shen
A1 Tyler D. Bold
A1 Ryan A. Langlois
YR 2020
UL http://biorxiv.org/content/early/2020/10/19/2020.10.19.343954.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.