Interferon Kappa Is Important for Keratinocyte Host Defense against Herpes Simplex Virus-1

Type I interferon kappa (IFN kappa) is selectively expressed in human keratinocytes. Herpes simplex virus-1 (HSV-1) is a human pathogen that infects keratinocytes and causes lytic skin lesions. Whether IFN kappa plays a role in keratinocyte host defense against HSV-1 has not been investigated. In this study, we found that IFN kappa mRNA expression was induced by addition of recombinant IFN kappa and poly (I:C); and its expression level was significantly greater than IFNa2, IFNb1, and IFNL1 in both undifferentiated and differentiated normal human epidermal keratinocytes (NHEKs) under resting and stimulation conditions. Although IFNe was expressed at a relatively higher level than other IFNs in resting undifferentiated NHEK, its expression level did not change after stimulation with recombinant IFN kappa and poly (I:C). HSV-1 infection inhibited gene expression of IFN kappa and IFNe in NHEK. Silencing IFN kappa in NHEK led to significantly enhanced HSV-1 replication in both undifferentiated and differentiated NHEK compared to scrambled siRNA-transfected cells, while the addition of recombinant IFN kappa significantly reduced HSV-1 replication in NHEK. In addition, we found that IFN kappa did not regulate protein expression of NHEK differentiation markers. Our results demonstrate that IFN kappa is the dominant type of IFNs in keratinocytes and it has an important function for keratinocytes to combat HSV-1 infection.