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Am J Physiol Lung Cell Mol Physiol
. 2020 Sep 9.
doi: 10.1152/ajplung.00374.2020. Online ahead of print.
Human coronaviruses 229E and OC43 replicate and induce distinct anti-viral responses in differentiated primary human bronchial epithelial cells
Su-Ling Loo 1 , Peter A B Wark 2 , Camille Esneau 3 , Kristy S Nichol 4 , Alan C-Y Hsu 5 , Nathan W Bartlett 6
Affiliations
- PMID: 32903043
- DOI: 10.1152/ajplung.00374.2020
Abstract
The recurrent emergence of novel, pathogenic coronaviruses (CoVs) SARS-CoV-1 (2002), MERS-CoV (2012) and most recently SARS-CoV-2 (2019) has highlighted the need for physiologically informative airway epithelial cell infection models for studying immunity to CoVs and development of anti-viral therapies. To address this, we developed an in-vitro infection model for two human coronaviruses; alphacoronavirus 229E-CoV (229E) and betacoronavirus OC43-CoV (OC43) in differentiated primary human bronchial epithelial cells (pBECs). Primary BECs from healthy subjects were grown at air liquid interface (ALI) and infected with 229E or OC43, and replication kinetics and time-course expression of innate immune mediators were assessed. OC43 and 229E-CoVs replicated in differentiated pBECs but displayed distinct replication kinetics: 229E replicated rapidly with viral load peaking at 24 hours post-infection, whilst OC43 replication was slower peaking at 7 days after infection. This was associated with diverse anti-viral response profiles defined by increased expression of type I/III interferons and interferon-stimulated genes (ISGs) by 229E compared to OC43. Understanding the host-virus interaction for previously established coronaviruses will give insight into pathogenic mechanisms underpinning SARS-CoV-2-induced respiratory disease and other future coronaviruses that may arise from zoonotic sources.
Keywords: 229E; OC43; coronavirus; epithelial cell; infection.