Type I and Type III Interferons Restrict SARS-CoV-2 Infection of Human Airway Epithelial Cultures

  1. Abigail Vanderheiden
  2. Philipp Ralfs
  3. Tatiana Chirkova
  4. Amit A. Upadhyay
  5. Matthew G. Zimmerman
  6. Shamika Bedoya
  7. Hadj Aoued
  8. Gregory M. Tharp
  9. Kathryn L. Pellegrini
  10. Candela Manfredi
  11. Eric Sorscher
  12. Bernardo Mainou
  13. Jenna L. Lobby
  14. Jacob E. Kohlmeier
  15. Anice C. Lowen
  16. Pei-Yong Shi
  17. Vineet D. Menachery
  18. Larry J. Anderson
  19. Arash Grakoui
  20. Steven E. Bosinger
  21. Mehul S. Suthar

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Abstract

The current pandemic of respiratory illness, COVID-19, is caused by a recently emerged coronavirus named SARS-CoV-2. This virus infects airway and lung cells causing fever, dry cough, and shortness of breath. Severe cases of COVID-19 can result in lung damage, low blood oxygen levels, and even death. As there are currently no vaccines approved for use in humans, studies of the mechanisms of SARS-CoV-2 infection are urgently needed. Our research identifies an excellent system to model SARS-CoV-2 infection of the human airways that can be used to test various treatments. Analysis of infection in this model system found that human airway epithelial cell cultures induce a strong proinflammatory cytokine response yet block the production of type I and III IFNs to SARS-CoV-2. However, treatment of airway cultures with the immune molecules type I or type III interferon (IFN) was able to inhibit SARS-CoV-2 infection. Thus, our model system identified type I or type III IFN as potential antiviral treatments for COVID-19 patients.

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  1. Version published to 10.1128/jvi.00985-20
  2. ScreenIT

    SciScore for 10.1101/2020.05.19.105437: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Cells were incubated with an anti-SARS-CoV-2 spike protein primary antibody conjugated to biotin (generously provided by Dr. Jens Wrammert, Emory University) for 2 hours at room temperature (RT), then with avidin-HRP conjugated secondary antibody for 1 hour at RT.
    anti-SARS-CoV-2 spike protein
    suggested: None
    avidin-HRP
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Viral titers were determined by plaque assay on VeroE6 cells (ATCC).
    VeroE6
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Vero cells were cultured in complete DMEM medium consisting of 1x DMEM (Corning Cellgro), 10% FBS, 25 mM HEPES Buffer (Corning Cellgro), 2 mM L-glutamine, 1mM sodium pyruvate, 1x Non-essential Amino Acids, and 1x antibiotics.
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    Software and Algorithms
    SentencesResources
    Viral genes were mapped to the FDAARGOS_983 strain of the 2019-nCoV/USA-WA1/2020 SARS-CoV2 isolate (GenBank Accession: MT246667.1), using STAR v2.7.3a (41).
    STAR
    suggested: (STAR, RRID:SCR_015899)
    Reads were normalized and differentially expressed genes were analyzed using DESeq2.
    DESeq2
    suggested: (DESeq, RRID:SCR_000154)
    Pathway analysis was performed using Cytoscape software.
    Cytoscape
    suggested: (Cytoscape, RRID:SCR_003032)
    The raw data of all RNA sequencing will be deposited into the Gene Expression Omnibus (GEO) repository and the accession number will be available following acceptance of this manuscript.
    Gene Expression Omnibus
    suggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)
    Statistical Analysis: Statistical analyses were performed using Graphpad Prism 8, ggplot2 R package, and GSEA software.
    Graphpad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)
    GSEA
    suggested: (SeqGSEA, RRID:SCR_005724)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2020.05.19.105437v1 on bioRxiv