Journal article
Uncovering strain- and age-dependent innate immune responses to SARS-CoV-2 infection in air-liquid-interface cultured nasal epithelia
JJY Chang, SL Grimley, BM Tran, G Deliyannis, C Tumpach, ANT Nguyen, E Steinig, JS Zhang, J Schröder, L Caly, J McAuley, SL Wong, SA Waters, TP Stinear, ME Pitt, D Purcell, E Vincan, LJM Coin
Iscience | CELL PRESS | Published : 2024
Abstract
Continuous assessment of the impact of SARS-CoV-2 on the host at the cell-type level is crucial for understanding key mechanisms involved in host defense responses to viral infection. We investigated host response to ancestral-strain and Alpha-variant SARS-CoV-2 infections within air-liquid-interface human nasal epithelial cells from younger adults (26–32 Y) and older children (12–14 Y) using single-cell RNA-sequencing. Ciliated and secretory-ciliated cells formed the majority of highly infected cell-types, with the latter derived from ciliated lineages. Strong innate immune responses were observed across lowly infected and uninfected bystander cells and heightened in Alpha-infection. Alpha ..
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Awarded by Stimson Miller Foundation
Funding Acknowledgements
We thank the Biological Optical Microscopy Platform (BOMP) at the University of Melbourne for their assistance. This research was supported by The University of Melbourne's Research Computing Services and the Petascale Campus Initiative. This research was undertaken using the LIEF HPC-GPGPU Facility hosted at the University of Melbourne. This Facility was established with the assistance of LIEF Grant LE170100200. Establishment of the ALI-HNEC was funded in part by philanthropic funding from the Kim Wright Foundation (awarded to E.V.) . B.M.T.'s salary is supported by a National Health and Medical Research Council (NHMRC) Ideas Grant (APP1181580) awarded to B.M.T. and E.V.. S.A.W. is supported by the UNSW Scientia program and the Australian National Health and Medical Research Council Ideas Grant (1188987) . J.C. was supported by the Miller Foundation and the Australian Government Research Training Program (RTP) scholarship. We gratefully acknowledge Dr. Jenny Anderson of the Computational Sciences Initiative (CSI) , The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, for the discussion of results and Dr. Hyun Jae Lee for guidance regarding single-cell analysis. Additionally, we wish to thank the Ramaciotti Center for Genomics for sequencing all Illumina libraries and Macrogen for running the microarrays for genotyping analysis. The graphical abstract was created with BioRender.com .