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J Proteome Res. 2022 Jan 04; doi: 10.1021/acs.jproteome.1c00783. Epub 2022 Jan 04.

Deep Time Course Proteomics of SARS-CoV- and SARS-CoV-2-Infected Human Lung Epithelial Cells (Calu-3) Reveals Strong Induction of Interferon-Stimulated Gene Expression by SARS-CoV-2 in Contrast to SARS-CoV.

Journal of proteome research

Marica Grossegesse, Daniel Bourquain, Markus Neumann, Lars Schaade, Jessica Schulze, Christin Mache, Thorsten Wolff, Andreas Nitsche, Joerg Doellinger

Affiliations

  1. Centre for Biological Threats and Special Pathogens: Highly Pathogenic Viruses (ZBS 1), Robert Koch Institute, 13353Berlin, Germany.
  2. Centre for Biological Threats and Special Pathogens, Robert Koch Institute, 13353Berlin, Germany.
  3. Influenza and Other Respiratory Viruses, Robert Koch Institute, Unit 17, 13353Berlin, Germany.
  4. Centre for Biological Threats and Special Pathogens: Proteomics and Spectroscopy (ZBS 6), Robert Koch Institute, 13353Berlin, Germany.

PMID: 34982558 DOI: 10.1021/acs.jproteome.1c00783

Abstract

Severe acute respiratory syndrome (SARS)-CoV and SARS-CoV-2 infections are characterized by remarkable differences, including infectivity and case fatality rate. The underlying mechanisms are not well understood, illustrating major knowledge gaps of coronavirus biology. In this study, protein expression of the SARS-CoV- and SARS-CoV-2-infected human lung epithelial cell line Calu-3 was analyzed using data-independent acquisition-mass spectrometry. This resulted in a comprehensive map of infection-related proteome-wide expression changes in human cells covering the quantification of 7478 proteins across four time points. Most notably, the activation of interferon type-I response was observed, which is surprisingly absent in several proteome studies. The data reveal that SARS-CoV-2 triggers interferon-stimulated gene expression much stronger than SARS-CoV, which reflects the already described differences in interferon sensitivity. Potentially, this may be caused by the enhanced abundance of the viral M protein of SARS-CoV in comparison to SARS-CoV-2, which is a known inhibitor of type I interferon expression. This study expands the knowledge on the host response to SARS-CoV-2 infections on a global scale using an infection model, which seems to be well suited to analyze the innate immunity.

Keywords: SARS-CoV-2; coronavirus; data-independent acquisition; interferon response; interferon-stimulated gene; proteomics

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