Tropism, replication competence, and cellular responses of HAdV-14p1 in human airway organoids.

Human adenovirus type 14p1 (HAdV-14p1) is associated with severe respiratory illness. Using human airway organoids, we characterized the cellular tropism, infection dynamics, and cellular response to HAdV-14p1, and evaluated the antiviral efficacy of cidofovir. HAdV-14p1 robustly infected and replicated in human airway organoids, particularly targeting ciliated, basal, and goblet cells. CCL5, CXCL10, CXCL11, and TNFSF13B were significantly upregulated upon HAdV-14p1 infection, indicating inflammatory activation. Pathway enrichment analysis revealed that upregulated genes were enriched in p53 signaling, cytokine-cytokine receptor interaction, and NOD-like receptor signaling pathways, whereas downregulated genes were linked to focal adhesion, tight junction, metabolic pathways, and oxidative phosphorylation pathways. Furthermore, treatment with cidofovir effectively inhibited viral replication with low cytotoxicity. Our findings highlight the robust replication and proinflammatory response that shape HAdV-14p1 pathogenesis and underscore the value of organoid systems in probing virus-host interactions and evaluating candidate antiviral strategies.