HUMAN CYTOMEGALOVIRUS INFECTION TRIGGERS THE INTERFERON RESPONSE VIA THE DNA SENSOR IFI16 IN HUMAN KERATINOCYTES

Human cytomegalovirus (HCMV), a member of the β-herpesvirus family, infects hosts for life despite a consistent multi-prolonged antiviral immune response that targets the infection. HCMV productively replicates in a broad range of cell types, including epithelial cells. Keratinocytes are the predominant epithelial cells of the epidermis, well equipped to recognize bacterial and viral pathogens. We investigated the capability of spontaneously immortalized human keratinocytes (NIKS) to support HCMV infection and replication. Growth kinetics and immunofluorescence analysis revealed that NIKS supported productive replication of HCMV clinical isolates (TR and VR1814), albeit with a retarded kinetics compared to that observed in cell lines used for HCMV production, such as Human Foreskin Fibroblasts (HFF). Inflammasome activation and Interferon production are key players in the innate immune response against HCMV infection. Whether such mechanisms are activated in keratinocytes by HCMV infection is poorly defined. In this study we demonstrate that Interferon type III (IFN-λ1), but not IFN type I production is stimulated during HCMV infection. Conversely, we did not observe the activated form of caspase-1, indicating that the inflammasome system is not significantly involved in keratinocytes immunity against HCMV. Moreover, IFI16 knockdown experiments revealed that IFI16 is responsible for inducing IFN-λ1 production in HCMV-infected keratinocytes. We are currently investigating the mechanisms of IFI16 rely on to activate IFN-λ1 pathway and the transcription factors triggered by IFI16 to activate IFN-λ1 promoter in keratinocytes.