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

Thao Vo, Kshitiz Paudel, Ishita Choudhary, Sonika Patial, View ORCID ProfileYogesh Saini
doi: https://doi.org/10.1101/2020.11.10.377408
Thao Vo
aDepartment of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA
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Kshitiz Paudel
aDepartment of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA
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Ishita Choudhary
aDepartment of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA
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Sonika Patial
aDepartment of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA
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Yogesh Saini
aDepartment of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA
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  • ORCID record for Yogesh Saini
  • For correspondence: ysaini@lsu.edu
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Abstract

Background SARS-CoV-2, a novel coronavirus, and the 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 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.

Objective To investigate the impact of ozone inhalation on the expression levels of signatures associated with host susceptibility to SARS-CoV-2.

Methods We analyzed lung tissues collected from mice that were sub-chronically exposed to air or 0.8ppm ozone for three weeks (4h/night, 5 nights/week), and analyzed the expression of signatures associated with host susceptibility to SARS-CoV-2.

Results SARS-CoV-2 entry into the host cells requires proteolytic priming by the host-derived protease, transmembrane protease serine 2 (TMPRSS2). 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.

Conclusions 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 mice-ozone-exposure based study informs the scientific community of the potentially detrimental effects of the ambient ozone levels determining the host susceptibility to SARS-CoV-2.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Funding: This work was supported by the National Institute of Environmental Health Sciences Grant R01ES030125 (to Y.S.).

  • Disclosures: The authors have no conflicts of interest to disclose.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted November 11, 2020.
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Ozone exposure upregulates the expression of host susceptibility protein TMPRSS2 to SARS-CoV-2
Thao Vo, Kshitiz Paudel, Ishita Choudhary, Sonika Patial, Yogesh Saini
bioRxiv 2020.11.10.377408; doi: https://doi.org/10.1101/2020.11.10.377408
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Ozone exposure upregulates the expression of host susceptibility protein TMPRSS2 to SARS-CoV-2
Thao Vo, Kshitiz Paudel, Ishita Choudhary, Sonika Patial, Yogesh Saini
bioRxiv 2020.11.10.377408; doi: https://doi.org/10.1101/2020.11.10.377408

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