Uncovering strain- and age-dependent innate immune responses to SARS-CoV-2 infection in air-liquid-interface cultured nasal epithelia

Authors:

• Chang, Jessie J.-Y.
• Grimley, Samantha L.
• Tran, Bang M.
• Deliyannis, Georgia
• Tumpach, Carolin
• Nguyen, An N.T.
• Steinig, Eike
• Zhang, JianShu
• Schröder, Jan
• Caly, Leon
• McAuley, Julie
• Wong, Sharon L.
• Waters, Shafagh A.
• Stinear, Timothy P.
• Pitt, Miranda E.
• Purcell, Damian
• Vincan, Elizabeth
• Coin, Lachlan J.M.

Details:

iScience, Volume 27, Issue 6, 2024-06-21

Article Link: Click here

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 highly infected cells showed increased expression of protein-refolding genes compared with ancestral-strain-infected cells in children. Furthermore, oxidative phosphorylation-related genes were down-regulated in bystander cells versus infected and mock-control cells, underscoring the importance of these biological functions for viral replication. Overall, this study highlights the complexity of cell-type-, age- and viral strain-dependent host epithelial responses to SARS-CoV-2.