Ozone exposure upregulates the expression of host susceptibility protein TMPRSS2 to SARS-CoV-2

  1. Thao Vo
  2. Kshitiz Paudel
  3. Ishita Choudhary
  4. Sonika Patial
  5. Yogesh Saini

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Abstract

SARS-CoV-2, a novel coronavirus and an etiologic agent for the current global health emergency, causes acute infection of the respiratory tract leading to severe disease and significant mortality. Ever since the start of SARS-CoV-2, also known as the COVID-19 pandemic, countless uncertainties have been revolving around the pathogenesis and epidemiology of the SARS-CoV-2 infection. While air pollution has been shown to be strongly correlated to increased SARS-CoV-2 morbidity and mortality, whether environmental pollutants such as ground-level ozone affects the susceptibility of individuals to SARS-CoV-2 is not yet established. To investigate the impact of ozone inhalation on the expression levels of signatures associated with host susceptibility to SARS-CoV-2, we analyzed lung tissues collected from mice that were sub-chronically exposed to air or 0.8 ppm ozone for three weeks (4 h/night, 5 nights/week), and analyzed the expression of signatures associated with host susceptibility to SARS-CoV-2. SARS-CoV-2 entry into the host cells is dependent on the binding of the virus to the host cellular receptor, angiotensin-converting enzyme (ACE2), and its subsequent proteolytic priming by the host-derived protease, transmembrane protease serine 2 (TMPRSS2). The Ace2 transcripts were significantly elevated in the parenchyma, but not in the extrapulmonary airways and alveolar macrophages, from ozone-exposed mice. The TMPRSS2 protein and Tmprss2 transcripts were significantly elevated in the extrapulmonary airways, parenchyma, and alveolar macrophages from ozone-exposed mice. A significant proportion of additional known SARS-CoV-2 host susceptibility genes were upregulated in alveolar macrophages and parenchyma from ozone-exposed mice. Our data indicate that the unhealthy levels of ozone in the environment may predispose individuals to severe SARS-CoV-2 infection. Given the severity of this pandemic and the challenges associated with direct testing of host-environment interactions in clinical settings, we believe that this ozone exposure-based study informs the scientific community of the potentially detrimental effects of the ambient ozone levels in determining the host susceptibility to SARS-CoV-2.

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  1. Version published to 10.1038/s41598-022-04906-8
  2. ScreenIT

    SciScore for 10.1101/2020.11.10.377408: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: All animal use procedures were performed after approval from the Institutional Animal Care and Use Committee (IACUC) of the Louisiana State University.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Rabbit polyclonal TMPRSS2 primary antibody (ab214462; Abcam Cambridge, MA) and mouse monoclonal alpha tubulin (T5168, Sigma-Aldrich, MO) were used.
    TMPRSS2
    suggested: None
    alpha tubulin
    suggested: None
    Protein bands were visualized using secondary antibodies (alexa fluor 680 Goat anti-rabbit IgG or Alexa fluor 800 Goat anti-mouse IgG) and acquired using Odyssey CLx, Imager (LI-COR, NE) 2.
    anti-rabbit IgG
    suggested: (Thermo Fisher Scientific Cat# A32808, RRID:AB_2762837)
    anti-mouse IgG
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    Animal husbandry, experimental design and ozone exposure: Seven-week-old C57BL/6 mice were procured from Jackson Laboratory (Bar Harbor, ME).
    C57BL/6
    suggested: None
    Software and Algorithms
    SentencesResources
    RNA isolation and quality assessment, Construction of sequencing library, RNA sequencing and Gene Expression Analyses, and Data Availability: The detailed methodologies have been previously published 1.
    Gene Expression Analyses
    suggested: None
    The raw data have been submitted to the Gene Expression Omnibus (GEO) database.
    Gene Expression Omnibus
    suggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)
    Statistical analyses were performed using GraphPad Prism 8.0 (GraphPad Software, La Jolla, CA).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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 did not find any issues relating to the usage of bar graphs.

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2020.11.10.377408v1 on bioRxiv