Woodsmoke particulates alter expression of antiviral host response genes in human nasal epithelial cells infected with SARS-CoV-2 in a sex-dependent manner

Abstract

We have previously shown that exposure to particulate air pollution, both from natural and anthropogenic sources, alters gene expression in the airways and increases susceptibility to respiratory viral infection. Additionally, we have shown that woodsmoke particulates (WSP) affect responses to influenza in a sex-dependent manner. In the present study, we used human nasal epithelial cells (hNECs) from both sexes to investigate how particulate exposure could modulate gene expression in the context of SARS-CoV-2 infection. We used diesel exhaust particulate (DEP) as well as WSP derived from eucalyptus or red oak wood. HNECs were exposed to particulates at a concentration of 22 g/cm2 for 2 h then immediately infected with SARS-CoV-2 at a MOI (multiplicity of infection) of 0.5. Exposure to particulates had no significant effects on viral load recovered from infected cells. Without particulate exposure, hNECs from both sexes displayed a robust upregulation of antiviral host response genes, though the response was greater in males. However, WSP exposure before infection dampened expression of genes related to the antiviral host response by 72 h post infection. Specifically, red oak WSP downregulated IFIT1, IFITM3, IFNB1, MX1, CCL3, CCL5, CXCL11, CXCL10, and DDX58, among others. After sex stratification of these results, we found that exposure to WSP prior to SARS-CoV-2 infection downregulated anti-viral gene expression in hNECs from females more so than males. These data indicate that WSP, specifically from red oak, alter virus-induced gene expression in a sex-dependent manner and potentially suppress antiviral host defense responses following SARS-CoV-2 infection.