Open AccessSingle cell resolution of SARS-CoV-2 tropism, antiviral responses, and susceptibility to therapies in primary human airway epithelium
Author(s) -
Jessica K. Fiege,
Joshua M. Thiede,
Hezkiel Nanda,
William E. Matchett,
Patrick J. Moore,
Noe Rico Montanari,
Beth K Thielen,
Jerry Daniel,
Emma Stanley,
Ryan C. Hunter,
Vineet D. Menachery,
Steven S. Shen,
Tyler D. Bold,
Ryan A. Langlois
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009292
Subject(s) - tropism , biology , respiratory epithelium , virology , tissue tropism , population , cell , immunology , immune system , pathogenesis , viral replication , interferon , flow cytometry , epithelium , virus , medicine , genetics , environmental health
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.