Interferon epsilon as a novel anti-viral agent in the testis [human]

The testis is susceptible to viral infections, which can impair fertility. Spermatogenic cells were thought to lack anti-viral defences, including interferon (IFN) or IFN-stimulated gene (ISG) expression. Challenging this dogma, we discovered that interferon-epsilon (IFNɛ), a type-I IFN first identified in female reproductive epithelia, is constitutively expressed by spermatogenic cells and macrophages in mouse and human testes. Moreover, mice lacking IFNɛ are more susceptible to viral epididymo-orchitis. The mechanisms of IFNɛ-mediated anti-viral protection in the testis were examined in this study. A vial of Sertoli cells isolated from human testis (HSerc) that were cryopreserved at passage one was purchased from ScienCell Research Laboratories, USA (Catalog #4520). The cells were infected with Zika virus (strain PRVABC59) at a multiplicity of infection (MOI) of 5 or 10. Cultures were treated with 100IU recombinant human IFNɛ 12h before infection (prophylactic-IFNɛ) or 1h after infection (therapeutic-IFNɛ), or diluent alone (controls). (IFNɛ was generated in house as described in Stifter et al. 2017; specific activity 3.62 x 104 IU/ml). Cells and media were harvested 24h or 48h post-infection for RNA-seq, qPCR, and plaque assays.