Abstract
A large body of evidence shows the harmful effects of cigarette smoke to oral and systemic health. More recently, a link between smoking and susceptibility to coronavirus disease 2019 (COVID-19) was proposed. COVID-19 is due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which uses the receptor ACE2 and the protease TMPRSS2 for entry into host cells, thereby infecting cells of the respiratory tract and the oral cavity. Here, we examined the effects of cigarette smoke on the expression of SARS-CoV-2 receptors and infection in human gingival epithelial cells (GECs). We found that cigarette smoke condensates (CSC) upregulated ACE2 and TMPRSS2 expression in GECs, and that CSC activated aryl hydrocarbon receptor (AhR) signaling in the oral cells. ACE2 was known to mediate SARS-CoV-2 internalization, and we demonstrate that CSC treatment potentiated the internalization of SARS-CoV-2 pseudovirus in GECs in an AhR-dependent manner. AhR depletion using small interference RNA decreased SARS-CoV-2 pseudovirus internalization in CSC-treated GECs compared with control GECs. Our study reveals that cigarette smoke upregulates SARS-CoV-2 receptor expression and infection in oral cells. Understanding the mechanisms involved in SARS-CoV-2 infection in cells of the oral cavity may suggest therapeutic interventions for preventing viral infection and transmission.
Highlights
Smoking harms nearly every organ in the body, and remains the leading cause of preventable disease, disability, and death in the United States [1,2]
We examined whether treatment with cigarette smoke condensates (CSC) at different concentrations [32] could modulate the expression of these proteins
Cell death was not detectable in our experiments after CSC treatment (Figure S1). These results confirm that gingival epithelial cells (GECs) express SARS-CoV-2 receptors, which are upregulated after CSC treatment
Summary
Smoking harms nearly every organ in the body, and remains the leading cause of preventable disease, disability, and death in the United States [1,2]. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in Wuhan (China) as the cause of a novel viral pneumonia [14]. The World Health Organization (WHO) announced that SARS-CoV-2 is the causative agent of COVID-19, and in March 2020 the WHO declared COVID-19 a pandemic [15]. This pandemic has had an unprecedented social and economic impact on the lives of billions of people worldwide, having caused over 3.8 million deaths and more than 178 million cases worldwide as of 22 June 2021 [16]
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