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

Abstract

Type I interferon kappa (IFNκ) 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 IFNκ plays a role in keratinocyte host defense against HSV-1 has not been investigated. In this study, we found that IFNκ mRNA expression was induced by addition of recombinant IFNκ 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 IFNκ and poly (I:C). HSV-1 infection inhibited gene expression of IFNκ and IFNe in NHEK. Silencing IFNκ 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 IFNκ significantly reduced HSV-1 replication in NHEK. In addition, we found that IFNκ did not regulate protein expression of NHEK differentiation markers. Our results demonstrate that IFNκ is the dominant type of IFNs in keratinocytes and it has an important function for keratinocytes to combat HSV-1 infection.

Swarms of chemically modified antiviral siRNA targeting herpes simplex virus infection in human corneal epithelial cells

“…Certainly, indirect downregulation of the studied markers due to modulation of an upstream function is likely. Nevertheless, at 44 hpi, HCE cells were able to induce significantly increased expression of IFN-β , IFN-κ and MxB to counteract the infection ( Fig 3A ), which might have in part hindered the increase in viral gene expression from 20 to 44 hpi ( S1 Fig ) as IFN-β , IFN-κ and MxB are antiviral [ 24 , 25 ].…”

Herpes Simplex Virus Type 1 Interactions with the Interferon System

“…While pDCs are usually absent in healthy skin, they infiltrate the dermis upon infection and interact with other immune cells in order to control viral replication [ 139 ]. It has recently been shown that in vitro, IFNκ is also secreted by human keratinocytes and blocking IFNκ expression enhances HSV-1 replication, indicating it may also play a role in controlling HSV-1 in herpes lesions [ 140 ]. Secreted type I IFN, among other cytokines, including IL12, IL15, and IL18, activate NK cells, which produce IFNγ, which plays an important protective role against both HSV-1 and HSV-2 infections [ 35 , 141 , 142 ].…”

Shared and Unique Features of Human Interferon-Beta and Interferon-Alpha Subtypes

“…Two IFN-I genes are selectively expressed in specific organs or by specific cell types: IFNϵ is hormonally regulated and primarily expressed in the female genital tract ( 4 ) and has recently been reviewed elsewhere. IFNκ is primarily expressed by keratinocytes ( 5 ) where it has recently been shown to have a role in protection against cutaneous herpes simplex virus ( 6 ), papilloma virus ( 7 ), and cutaneous lupus erythematosus ( 8 ). Like IFNϵ, IFNκ is constitutively expressed ( 9 ).…”