Temperature-dependent replication and sensitivity to innate immunity of human coronavirus HKU1
Abstract
The human coronavirus HKU1, causing common colds and occasionally severe illness, remains largely uncharacterized because it has not been successfully grown on immortalized cells. Here, we identify Caco2 cells overexpressing TMPRSS2, the HKU1 receptor, as being highly permissive to infection. HKU1 replicates efficiently, forms syncytia and releases infectious progeny in these cells at 33 °C, the temperature of the nasal cavity, but is attenuated at 37 °C. Viral entry occurs similarly at both temperatures, but subsequent viral RNA synthesis is enhanced at 33 °C. Released virions display higher stability at 33 °C. In Caco2 and primary epithelial nasal cells, HKU1 is sensitive to interferons (IFN), but induction of IFN stimulated genes, such as IFN-Induced Transmembrane Proteins (IFITMs), is delayed at 33 °C. Once expressed, IFITMs comparably inhibit HKU1 fusion at both temperatures. In contrast, SARS-CoV-2 robustly replicates at 37 °C. Thus, cellular permissiveness, innate immunity and viral properties collectively explain why HKU1 replicates more efficiently at nasal temperature. Our results highlight temperature-sensitivity disparities between coronaviruses, likely associated to different pathogenic outcomes.
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BibTeX
@article{buchrieser2026temperaturedependent,
title = {{Temperature-dependent replication and sensitivity to innate immunity of human coronavirus HKU1}},
author = {Julian Buchrieser and Eva Thuillier and Jeanne Postal and Amélie Wileveau and Florence Guivel-Benhassine and Isabelle Staropoli and Nell Saunders and Delphine Planas and Jamie Sugrue and Vincent Bondet and Ignacio Fernández and François Bontems and Françoise Porrot and Chloé Petiot and Matthieu Prot and Martin Jungbauer-Groznica and Laurence Arowas and Vincent Michel and Catherine Blanc and Sophie Trouillet-Assant and Timothée Bruel and Félix Rey and Marie-Anne Rameix-Welti and Nicoletta Casartelli and Arnaud Fontanet and Michael White and Darragh Duffy and Etienne Simon-Lorière and Olivier Schwartz},
journal = {Nature Communications},
year = {2026},
month = jul,
doi = {10.1038/s41467-026-75779-y},
url = {https://pasteur.hal.science/pasteur-05738336v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Temperature-dependent replication and sensitivity to innate immunity of human coronavirus HKU1
AU - Julian Buchrieser
AU - Eva Thuillier
AU - Jeanne Postal
AU - Amélie Wileveau
AU - Florence Guivel-Benhassine
AU - Isabelle Staropoli
AU - Nell Saunders
AU - Delphine Planas
AU - Jamie Sugrue
AU - Vincent Bondet
AU - Ignacio Fernández
AU - François Bontems
AU - Françoise Porrot
AU - Chloé Petiot
AU - Matthieu Prot
AU - Martin Jungbauer-Groznica
AU - Laurence Arowas
AU - Vincent Michel
AU - Catherine Blanc
AU - Sophie Trouillet-Assant
AU - Timothée Bruel
AU - Félix Rey
AU - Marie-Anne Rameix-Welti
AU - Nicoletta Casartelli
AU - Arnaud Fontanet
AU - Michael White
AU - Darragh Duffy
AU - Etienne Simon-Lorière
AU - Olivier Schwartz
PY - 2026
DA - 2026/07/27
JO - Nature Communications
DO - 10.1038/s41467-026-75779-y
UR - https://pasteur.hal.science/pasteur-05738336v1
AB - The human coronavirus HKU1, causing common colds and occasionally severe illness, remains largely uncharacterized because it has not been successfully grown on immortalized cells. Here, we identify Caco2 cells overexpressing TMPRSS2, the HKU1 receptor, as being highly permissive to infection. HKU1 replicates efficiently, forms syncytia and releases infectious progeny in these cells at 33 °C, the temperature of the nasal cavity, but is attenuated at 37 °C. Viral entry occurs similarly at both temperatures, but subsequent viral RNA synthesis is enhanced at 33 °C. Released virions display higher stability at 33 °C. In Caco2 and primary epithelial nasal cells, HKU1 is sensitive to interferons (IFN), but induction of IFN stimulated genes, such as IFN-Induced Transmembrane Proteins (IFITMs), is delayed at 33 °C. Once expressed, IFITMs comparably inhibit HKU1 fusion at both temperatures. In contrast, SARS-CoV-2 robustly replicates at 37 °C. Thus, cellular permissiveness, innate immunity and viral properties collectively explain why HKU1 replicates more efficiently at nasal temperature. Our results highlight temperature-sensitivity disparities between coronaviruses, likely associated to different pathogenic outcomes.
SN - 2041-1723
SN - 2041-1723
ER -