Contemporary seasonal human coronaviruses display differences in cellular tropism compared to laboratory-adapted reference strains
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(Published version)
Date
2025
Authors
Gartner, M.J.
Smith, M.L.
Dapat, C.
Liaw, Y.W.
Tran, T.
Suryadinata, R.
Chen, J.
Sun, G.
Shepherd, R.A.
Taiaroa, G.
Editors
Gallagher, T.
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Journal article
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Journal of Virology, 2025; 99(9):e0068425-1-e0068425-22
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Matthew J. Gartner, Monique L. Smith, Clyde Dapat, Yi Wen Liaw, Thomas Tran, Randy Suryadinata, Joseph Chen, Guizhi Sun, Rory A. Shepherd, George Taiaroa, Michael Roche, Wen Shi Lee, Philip Robinson, Jose M. Polo, Kanta Subbarao, Jessica A. Neil
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Abstract
Seasonal human coronaviruses (sHCoVs) cause 15%–30% of common colds. The reference strains used for research were isolated decades ago and have been passaged extensively, but contemporary sHCoVs have been challenging to study as they are notoriously difficult to grow in standard immortalized cell lines. Here, we addressed these issues by utilizing primary human nasal epithelial cells (HNECs) and immortalized human bronchial epithelial cells (BCi) differentiated at an air-liquid interface, as well as human embryonic stem cell-derived alveolar type II (AT2) cells to recover contemporary sHCoVs from human nasopharyngeal specimens. From 21 specimens, we recovered four HCoV-229e, three HCoV-NL63, and eight HCoV-OC43 viruses. All contemporary sHCoVs showed sequence differences from lab-adapted CoVs, particularly within the spike gene. Evidence of nucleotide changes in the receptor binding domains within HCoV-229e and detection of recombination for both HCoV-229e and HCoV-OC43 isolates was also observed. Importantly, we developed methods for the amplification of high-titer stocks of HCoV-NL63 and HCoV-229e that maintained sequence identity, and we established methods for the titration of contemporary sHCoV isolates. Comparison of lab-adapted and contemporary strains in immortalized cell lines and airway epithelial cells revealed differences in cell tropism, growth kinetics, and cytokine production between lab-adapted and contemporary sHCoV strains. These data confirm that contemporary sHCoVs differ from lab-adapted reference strains and, using the methods established here, should be used for the study of CoV biology and evaluation of medical countermeasures.
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© 2025 Gartner et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.