Tropism of and Innate Immune Responses to the Novel Human Betacoronavirus Lineage C Virus in Human Ex Vivo Respiratory Organ Cultures

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  • Renee W. Y. Chan
    • Other Affiliation: Centre of Influenza Research and School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China ; Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China
  • Michael C. W. Chan
    • Other Affiliation: Centre of Influenza Research and School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Sudhakar Agnihothram
    • Other Affiliation: Departments of Epidemiology and Microbiology and Immunology, Gillings School of Global Public Health, and School of Medicine, The University of North Carolina, Chapel Hill, North Carolina, USA
  • Louisa L. Y. Chan
    • Other Affiliation: Centre of Influenza Research and School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Denise I. T. Kuok
    • Other Affiliation: Centre of Influenza Research and School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Joanne H. M. Fong
    • Other Affiliation: Centre of Influenza Research and School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Y. Guan
    • Other Affiliation: Centre of Influenza Research and School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China ; State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
  • Leo L. M. Poon
    • Other Affiliation: Centre of Influenza Research and School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China ; State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
  • Ralph S. Baric
    • Other Affiliation: Departments of Epidemiology and Microbiology and Immunology, Gillings School of Global Public Health, and School of Medicine, The University of North Carolina, Chapel Hill, North Carolina, USA
  • John M. Nicholls
    • Other Affiliation: Centre of Influenza Research and School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China ; Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China
  • J. S. Malik Peiris
    • Other Affiliation: Centre of Influenza Research and School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China ; State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
Abstract
  • Since April 2012, there have been 17 laboratory-confirmed human cases of respiratory disease associated with newly recognized human betacoronavirus lineage C virus EMC (HCoV-EMC), and 7 of them were fatal. The transmissibility and pathogenesis of HCoV-EMC remain poorly understood, and elucidating its cellular tropism in human respiratory tissues will provide mechanistic insights into the key cellular targets for virus propagation and spread. We utilized ex vivo cultures of human bronchial and lung tissue specimens to investigate the tissue tropism and virus replication kinetics following experimental infection with HCoV-EMC compared with those following infection with human coronavirus 229E (HCoV-229E) and severe acute respiratory syndrome coronavirus (SARS-CoV). The innate immune responses elicited by HCoV-EMC were also investigated. HCoV-EMC productively replicated in human bronchial and lung ex vivo organ cultures. While SARS-CoV productively replicated in lung tissue, replication in human bronchial tissue was limited. Immunohistochemistry revealed that HCoV-EMC infected nonciliated bronchial epithelium, bronchiolar epithelial cells, alveolar epithelial cells, and endothelial cells. Transmission electron microscopy showed virions within the cytoplasm of bronchial epithelial cells and budding virions from alveolar epithelial cells (type II). In contrast, there was minimal HCoV-229E infection in these tissues. HCoV-EMC failed to elicit strong type I or III interferon (IFN) or proinflammatory innate immune responses in ex vivo respiratory tissue cultures. Treatment of human lung tissue ex vivo organ cultures with type I IFNs (alpha and beta IFNs) at 1 h postinfection reduced the replication of HCoV-EMC, suggesting a potential therapeutic use of IFNs for treatment of human infection.
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  • Article
Rights statement
  • In Copyright
Journal title
  • Journal of Virology
Journal volume
  • 87
Journal issue
  • 12
Page start
  • 6604
Page end
  • 6614
Language
  • English
ISSN
  • 0022-538X
  • 1070-6321
  • 1098-5514
Publisher
  • American Society for Microbiology

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