Type I Interferon and Interferon-stimulated Gene Expression in Oral Epithelial Cells

Oral epithelial cells (OEC) represent the first site of host interaction with viruses that infect the body through the oral route; however, their innate antiviral defense mechanisms yet to be defined. Previous studies have determined that OEC express pathogen-, damage-, or danger-associated molecular patterns (PAMPs or DAMPs), but their expression of key antiviral innate immune mediators, including type I interferons (type I IFN) and interferon-stimulated genes (ISGs) has not been studied extensively. We used the oral keratinocyte cell line, OKF6/TERT1, in the presence and absence of the viral mimics poly(I:C) and unmethylated CpG DNA, to define the expression of type I IFN and ISGs. We identified the basal expression of novel type I IFN genes IFNE and IFNK, while IFNB1 was induced by viral mimics, through the nuclear translocation of IRF3. Numerous ISGs were expressed at basal levels in OEC, with an apparent correlation between high expression and antiviral activity at the earlier stages of viral infection. Stimulation of OECs with poly(I:C) led to selective induction of ISGs, including MX1, BST2, PML, RSAD2, ISG15, and ZC3HAV1. Together, our results demonstrate that OECs exhibit a robust innate antiviral immune defense profile, which is primed to address a wide variety of pathogenic viruses that are transmitted orally.