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

Thao Vo,Sonika Patial,Ishita Choudhary,Yogesh Saini,Kshitiz Paudel

doi:10.1038/s41598-022-04906-8

Thao Vo, Sonika Patial + Show 3 more

Open Access

https://doi.org/10.1038/s41598-022-04906-8

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Journal: Scientific Reports	Publication Date: Jan 25, 2022
Citations: 7	License type: open-access

Affiliation: Louisiana State University

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.

Highlights

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
The host susceptibility to SARS-CoV-2 could vary based on the expression of the host susceptibility proteins including ACE2 and T MPRSS23–5
While it is already known that the unhealthy levels of ozone increase the risk for developing cardiopulmonary health problems[14,15,16,17,18,19,20], it is unclear whether the ambient ozone levels regulate the expression of host susceptibility proteins to SARS-CoV-2 and, in turn, account for the varied susceptibilities of the human population to SARS-CoV-2

Summary

Introduction

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. The mRNA expression levels of 33 known SARS-CoV-2 host susceptibility genes were assessed in three lung tissue compartments using RNASeq approach.

Results

Conclusion