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

臭氧暴露上调宿主对 SARS-CoV-2 的易感蛋白 TMPRSS2 的表达

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

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.

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.

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.

Objective

To investigate the impact of ozone inhalation on the expression levels 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.

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