RT Journal Article SR Electronic T1 Single-cell analysis of upper airway cells reveals host-viral dynamics in influenza infected adults JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.04.15.042978 DO 10.1101/2020.04.15.042978 A1 Yuming Cao A1 Zhiru Guo A1 Pranitha Vangala A1 Elisa Donnard A1 Ping Liu A1 Patrick McDonel A1 Jose Ordovas-Montanes A1 Alex K. Shalek A1 Robert W. Finberg A1 Jennifer P. Wang A1 Manuel Garber YR 2020 UL http://biorxiv.org/content/early/2020/04/17/2020.04.15.042978.abstract AB Influenza virus infections are major causes of morbidity and mortality. Research using cultured cells, bulk tissue, and animal models cannot fully capture human disease dynamics. Many aspects of virus-host interactions in a natural setting remain unclear, including the specific cell types that are infected and how they and neighboring bystander cells contribute to the overall antiviral response. To address these questions, we performed single-cell RNA sequencing (scRNA-Seq) on cells from freshly collected nasal washes from healthy human donors and donors diagnosed with acute influenza during the 2017-18 season. We describe a previously uncharacterized goblet cell population, specific to infected individuals, with high expression of MHC class II genes. Furthermore, leveraging scRNA-Seq reads, we obtained deep viral genome coverage and developed a model to rigorously identify infected cells that detected influenza infection in all epithelial cell types and even some immune cells. Our data revealed that each donor was infected by a unique influenza variant and that each variant was separated by at least one unique non-synonymous difference. Our results demonstrate the power of massively-parallel scRNA-Seq to study viral variation, as well as host and viral transcriptional activity during human infection.Competing Interest StatementThe authors have declared no competing interest.