Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus

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  • Laurence Josset
    • Other Affiliation: Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington, USA
  • Vineet D. Menachery
    • Other Affiliation: Department of Epidemiology and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  • Lisa E. Gralinski
    • Other Affiliation: Department of Epidemiology and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  • Sudhakar Agnihothram
    • Other Affiliation: Department of Epidemiology and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  • Pavel Sova
    • Other Affiliation: Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington, USA
  • Victoria S. Carter
    • Other Affiliation: Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington, USA
  • Boyd L. Yount
    • Other Affiliation: Department of Epidemiology and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  • Rachel L. Graham
    • Other Affiliation: Department of Epidemiology and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  • Ralph S. Baric
    • Other Affiliation: Department of Epidemiology and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  • Michael G. Katze
    • Other Affiliation: Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington, USA
Abstract
  • A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not use the same receptor. Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. HCoV-EMC was able to replicate as efficiently as SARS-CoV in Calu-3 cells and similarly induced minimal transcriptomic changes before 12 h postinfection. Later in infection, HCoV-EMC induced a massive dysregulation of the host transcriptome, to a much greater extent than SARS-CoV. Both viruses induced a similar activation of pattern recognition receptors and the interleukin 17 (IL-17) pathway, but HCoV-EMC specifically down-regulated the expression of several genes within the antigen presentation pathway, including both type I and II major histocompatibility complex (MHC) genes. This could have an important impact on the ability of the host to mount an adaptive host response. A unique set of 207 genes was dysregulated early and permanently throughout infection with HCoV-EMC, and was used in a computational screen to predict potential antiviral compounds, including kinase inhibitors and glucocorticoids. Overall, HCoV-EMC and SARS-CoV elicit distinct host gene expression responses, which might impact in vivo pathogenesis and could orient therapeutic strategies against that emergent virus.
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  • Article
Rights statement
  • In Copyright
Journal title
  • MBio
Journal volume
  • 4
Journal issue
  • 3
Page start
  • 1
Page end
  • 11
Language
  • English
ISSN
  • 2150-7511
  • 2161-2129
Publisher
  • American Society for Microbiology

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