Seasonal H1N1 influenza A virus preferentially infects a pre-existing ciliogenesis-primed secretory cell state

von Kempis, J.; Leary, P.; Opitz, L.; Stertz, S.

doi:10.64898/2026.11.04.764425

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bioRxiv · 10.64898/2026.11.04.764425

Seasonal H1N1 influenza A virus preferentially infects a pre-existing ciliogenesis-primed secretory cell state

von Kempis, J.·Leary, P.·Opitz, L.·Stertz, S.

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Abstract

Influenza A viruses (IAV) infect secretory and ciliated cells of the human airway epithelium , but whether all cells within one cell type are equally susceptible to infection remains unresolved. Here, single-cell RNA sequencing analysis of primary human bronchial epithelial cultures from three donors identified preferential infection of a transcriptionally distinct subpopulation of secretory cells by seasonal H1N1 IAV A/Hawaii/70/2019 . Genes upregulated in this subpopulation showed enrichment for cilium-related gene ontology terms. In an ex post facto approach, this enrichment persisted after excluding genes differentially expressed between infected and mock-treated samples, including those identified in secretory cell-specific comparisons. Single-cell analysis further revealed no significant increase in ciliogenesis scores in infected secretory cells compared to mock infected cells at 6 hours post-infection , arguing against infection-induced activation of the canonical ciliogenesis programme during the initial viral replication cycle . Collectively, these results support preferential infection of ciliogenesis-primed secretory cells and refine IAV tropism beyond cell type to encompass epithelial differentiation state.

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von Kempis, J., Leary, P., Opitz, L., Stertz, S.. 2026-11-09. Seasonal H1N1 influenza A virus preferentially infects a pre-existing ciliogenesis-primed secretory cell state. https://doi.org/10.64898/2026.11.04.764425

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