Type III interferons (IFN-λ1–IFN-λ3) exert highly circumscribed antiviral effects dictated mainly by the limited expression of their receptor, IFNLR1, on mucosal epithelium. In PLoS Biology, Robek and colleagues reveal the epigenetic mechanisms that control this restricted pattern of IFNLR1 expression. The amount of methylation of the IFNLR1 promoter inversely correlates with the expression of this receptor. Conversely, as gene expression is positively regulated by acetylation, knockdown or chemical inhibition of histone deacetylases increases the acetylation and expression of IFNLR1. Cells that are normally insensitive to IFN-λ can be made responsive by inhibition of histone deacetylases and can thereby be rendered resistant to viral infection. Acetylation of the IFNLR1 promoter then allows access of the transcription factor NF-Y, which controls IFNLR1 expression. Selectively controlling expression of IFNLR1 through the use of small-molecule drugs may be useful in sensitizing cells to the antiviral effects of type III interferons.

PLoS Biol (7 January 2014) doi:10.1371/journal.pbio.1001758