Temperature and developmental stage govern intestinal susceptibility to human coronavirus 229E

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 °C and 32 °C, 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 °C, HCoV-229E replicates efficiently in enteroids from all donor ages and releases high titers of infectious progeny. In contrast, at 37 °C, 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-host interactions and reveal temperature- and age-dependent determinants governing intestinal permissiveness to this seasonal coronavirus.

Authors

Institutions

Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2026-06-24
DOI
https://doi.org/10.1073/pnas.2600632123
Primary Topic
COVID-19 Clinical Research Studies
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Temperature and developmental stage govern intestinal susceptibility to human coronavirus 229E

Artur Szczepański, Justyna Rymarowicz, Michał Pędziwiatr, Aleksandra Synowiec et al.
Proceedings of the National Academy of Sciences
COVID-19 Clinical Research Studies
article

Temperature and developmental stage govern intestinal susceptibility to human coronavirus 229E

Artur Szczepański, Justyna Rymarowicz, Michał Pędziwiatr, Aleksandra Synowiec, Madison S. Strine, Carlemi Calitz, Izabela Dróźdż, Matthias Zilbauer, Dasja Pajkrt, Laurensius Kevin Lie, M. Bochenek, Liza Konnikova, Agnieszka Robaszkiewicz, Renata B. Filler, Adithya Sridhar, Nina Johannesson, Heng‐Chang Chen, Krzysztof Pyrć, Katarzyna Owczarek, Maciej Borowiec, Craig B. Wilen, Katja C. Wolthers, Michał Pietrusiński, Nina Mickiewicz
article en

Abstract

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 °C and 32 °C, 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 °C, HCoV-229E replicates efficiently in enteroids from all donor ages and releases high titers of infectious progeny. In contrast, at 37 °C, 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-host interactions and reveal temperature- and age-dependent determinants governing intestinal permissiveness to this seasonal coronavirus.

Proceedings of the National Academy of SciencesVol. 123(26)
Jagiellonian University (PL), Amsterdam UMC Location University of Amsterdam (NL), Yale University (US), University of Łódź (PL), Cambridge School (PT), Emma Kinderziekenhuis (NL), Medical University of Lodz (PL), Łukasiewicz Research Network – PORT Polish Center for Technology Development (PL), Amsterdam University Medical Centers (NL), Institute of Infection and Immunity (CA), University of Amsterdam (NL)
EU4Health, Polsko-Amerykanska Komisja Fulbrighta, Narodowe Centrum Nauki, Horizon 2020 Framework Programme
Good health and well-being
Openalex Percentile: Top 7%
COVID-19 Clinical Research Studies
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.