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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,6,30]]},"abstract":"<jats:p>Human coronaviruses have been primarily associated with upper respiratory tract infections, yet cases of gastrointestinal symptoms in COVID-19 patients have highlighted their potential to cause systemic disease. Here, we detail the infection of intestinal epithelia by an endemic, low-pathogenic human coronavirus, human alphacoronavirus 229E, using patient-derived human intestinal enteroids (HIEs) from donors of various ages. Using fetal, pediatric, and adult HIEs, we investigated how physiologically relevant temperatures: 37 \u00b0C and 32 \u00b0C, reflecting gastrointestinal and upper-airway conditions, respectively, modulate epithelial responses and viral infection dynamics. We show that there is temperature-dependent transcriptional reprogramming, indicating strong temperature-dependent regulation of virus replication and epithelial responses. Among the seasonal coronaviruses tested, only HCoV-229E productively infects HIEs. At 32 \u00b0C, HCoV-229E replicates efficiently in enteroids from all donor ages and releases high titers of infectious progeny. In contrast, at 37 \u00b0C, productive replication is largely confined to fetal and a subset of pediatric tissues, revealing a developmental and temperature-sensitive restriction on infection. Confocal and flow cytometry analyses identify enterocytes as the primary target cells for HCoV-229E. Furthermore, we show that camostat, a serine protease inhibitor, significantly reduces HCoV-229E replication in HIEs, confirming a critical role for host serine protease activity. Collectively, these findings establish HIEs as a relevant model for HCoV-229E\u2013host interactions and reveal temperature- and age-dependent determinants governing intestinal permissiveness to this seasonal coronavirus.<\/jats:p>","DOI":"10.1073\/pnas.2600632123","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T17:42:04Z","timestamp":1782322924000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Temperature and developmental stage govern intestinal susceptibility to human coronavirus 229E"],"prefix":"10.1073","volume":"123","author":[{"given":"Aleksandra","family":"Synowiec","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03bqmcz70","id-type":"ROR","asserted-by":"publisher"}],"name":"Virogenetics Laboratory of Virology, Ma\u0142opolska Centre of Biotechnology, Jagiellonian University","place":["Krak\u00f3w, 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