Uncovering strain- and age- dependent differences in innate immune response to SARS-CoV-2 infection in nasal epithelia using combined short and long-read scRNA-seq

Chang, J. J.-Y.; Grimley, S.; Tran, B.; Deliyannis, G.; Tumpach, C.; Stinear, T. P.; Pitt, M. E.; Vincan, E.; Coin, L. J. M.

doi:10.1101/2023.03.04.531075

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bioRxiv · 10.1101/2023.03.04.531075

Uncovering strain- and age- dependent differences in innate immune response to SARS-CoV-2 infection in nasal epithelia using combined short and long-read scRNA-seq

Chang, J. J.-Y.·Grimley, S.·Tran, B.·Deliyannis, G.·Tumpach, C.·Stinear, T. P.·Pitt, M. E.·Vincan, E.·Coin, L. J. M.

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Abstract

Assessing the impact of SARS-CoV-2 variants on the host is crucial with continuous emergence of new variants. We employed single-cell sequencing to investigate host transcriptomic response to ancestral and Alpha-strain SARS-CoV-2 infections within air-liquid-interface human nasal epithelial cells from adults and adolescents. Strong innate immune responses were observed across lowly-infected and bystander cell-types, and heightened in Alpha-infection. Contrastingly, the innate immune response of highly-infected cells was like mock-control cells. Alpha highly-infected cells showed increased expression of protein refolding genes compared with ancestral-strain-infected adolescent cells. Oxidative phosphorylation- and translation-related genes were down-regulated in bystander cells versus infected and mock-control cells, suggesting that the down-regulation is protective and up-regulation supports viral activity. Infected adult cells revealed up-regulation of these pathways compared with infected adolescents, implying enhanced pro-viral states in infected adults. Overall, this highlights the complexity of cell-type-, age- and viral-strain-dependent host epithelial responses to SARS-CoV-2 and the value of air-liquid-interface cultures.

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Chang, J. J.-Y., Grimley, S., Tran, B., Deliyannis, G., Tumpach, C., Stinear, T. P., Pitt, M. E., Vincan, E., Coin, L. J. M.. 2023-03-06. Uncovering strain- and age- dependent differences in innate immune response to SARS-CoV-2 infection in nasal epithelia using combined short and long-read scRNA-seq. https://doi.org/10.1101/2023.03.04.531075

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