Coronaviruses and the human airway: a universal system for virus-host interaction studies

Abstract

Human coronaviruses (HCoVs) are large RNA viruses that infect the human respiratory tract. The emergence of both Severe Acute Respiratory Syndrome and Middle East Respiratory syndrome CoVs as well as the yearly circulation of four common CoVs highlights the importance of elucidating the different mechanisms employed by these viruses to evade the host immune response, determine their tropism and identify antiviral compounds. Various animal models have been established to investigate HCoV infection, including mice and non-human primates. To establish a link between the research conducted in animal models and humans, an organotypic human airway culture system, that recapitulates the human airway epithelium, has been developed. Currently, different cell culture systems are available to recapitulate the human airways, including the Air-Liquid Interface (ALI) human airway epithelium (HAE) model. Tracheobronchial HAE cultures recapitulate the primary entry point of human respiratory viruses while the alveolar model allows for elucidation of mechanisms involved in viral infection and pathogenesis in the alveoli. These organotypic human airway cultures represent a universal platform to study respiratory virus-host interaction by offering more detailed insights compared to cell lines. Additionally, the epidemic potential of this virus family highlights the need for both vaccines and antivirals. No commercial vaccine is available but various effective antivirals have been identified, some with potential for human treatment. These morphological airway cultures are also well suited for the identification of antivirals, evaluation of compound toxicity and viral inhibition.

Fig. 1

Human airway epithelial cell culture models and HCoV receptor distribution. a: Schematic representation of human tracheobronchial cells at air-liquid interface (ALI). They form a pseudostratified epithelial layer containing different cell types. b: Schematic representation of human alveolar cells at ALI that form single squamous epithelium containing only two cells types, alveolar type I and II cells. c: Illustration of the mode of infection, release and associated cell tropism of the six human coronaviruses (HCoVs) in the human airway epithelial cell culture model. SARS-CoV, HCoV-NL63, HCoV-OC43 and HCoV-HKU1 infect ciliated cells but the receptors for HCoV-HKU1 and HCoV-OC43 are currently unknown. HCoV-229E and MERS-CoV infect non-ciliated cells using different receptors