Decreasing the activity of DOT1L (DOT1 like histone lysine methyltransferase) through silencing or an inhibitor preferentially suppressed the production of interleukin 6 (IL-6) and interferon β (IFN-β) but not of tumor necrosis factor α (TNF-α) in macrophages triggered by Toll-like receptor (TLR) ligands or virus infection. This evidence concerns the gene DOT1L and viral infectious disease.