biostudies-literatureUnknown29(1)Guo WHuman 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 oxidativeiScience114323https://www.ebi.ac.uk/biostudies/studies/S-EPMC12765093biostudies-literatureTropism, replication competence, and cellular responses of HAdV-14p1 in human airway organoids.PMC12765093Peng XChen QLiu LLiang YGuo WLin WLin YLi LWen TLi YYang YLin CCui FWang YChen RZhou JDeng YfalseTropism, 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 oxidative2026-01-01T00:00:00Z2026 Jan2026-06-10T04:58:49.586Z2026-06-10T03:07:39.239ZS-EPMC127650934149246310.1016/j.isci.2025.114323