Interferons inhibit Ebola virus infection of human keratinocytes

Orthoebolavirus zairense, or Zaire Ebola virus (EBOV) is a species within the virus family Filoviridae, a group of viruses that can cause severe disease in humans characterized by hemorrhagic shock, coagulation abnormalities, and severe inflammation. While tissue macrophages are critical targets early during EBOV infection, other cell types support viral replication as disease progresses. At late stages of infection, infectious EBOV is found on the surface of the skin, which may be a critical source of infectious virus transmitted be-tween individuals during outbreaks. Human skin contains a number of cellular targets of EBOV, including keratinocytes. Here, we demonstrate EBOV infection of telomer-ase-immortalized normal human skin keratinocytes (NHSK-1) as well as EBOV?VP30 in-fection of NHSK-1 cells that were stably complemented with the EBOV transcription factor VP30. Infection with EBOV?VP30 did not elicit detectable endogenous interferon re-sponses, however, exogenous pre-treatment of NHSK-1 cells with type I, II, and III inter-feron (IFN) inhibited EBOV?VP30 infection and infection of an additional low contain-ment model of EBOV, rVSV/EBOV GP, in a dose-dependent manner. Analysis of the transcriptome of IFN-treated keratinocytes identified multiple genes unique to each IFN and a subset of ISGs upregulated by each IFN. Our results indicate that ISGs induced by IFN pre-treatment of keratinocytes can reduce infection, underlining possible anti-EBOV ISGs for development of EBOV-targeting therapeutics. Overall design: RNA-seq profiling of the transcriptome of telomerase-immortalized human keratinocytes at 6 or 24 hours following treatment with IFN-ß, IFN-?, IFN-a, or IFN-?.