Contemporary seasonal human coronaviruses display differences in cellular tropism compared to laboratory-adapted reference strains

Abstract

Zoonotic coronaviruses have caused significant public health emergencies. The occurrence of a similar spillover event in the future is likely, and efforts to further understand coronavirus biology should be a high priority. Several seasonal coronaviruses circulate within the human population. Efforts to study these viruses have been limited to reference strains isolated decades ago due to the difficulty in isolating clinical isolates. Here, we use human airway and alveolar epithelial cultures to recover contemporary isolates of human coronaviruses HCoV-NL63, HCoV-229e, and HCoV-OC43. We establish methods to make high-titer stocks and titrate HCoV-229e and HCoV-NL63 isolates. We show that contemporary isolates of HCoV-NL63 and HCoV-OC43 have a different tropism within the respiratory epithelium compared to lab-adapted strains. Although HCoV-229e clinical and lab-adapted strains similarly infect the respiratory epithelium, differences in host response and replication kinetics are observed. Using the methods developed here, future research should include contemporary isolates when studying coronavirus biology.