Infection with ΔE3L, but not WT vaccinia or E3LΔ83N, induced a vigorous antiviral innate immune response in murine keratinocytes via MAVS (mitochondrial antiviral signaling protein, an adaptor for cytosolic RNA sensors RIG-I and MDA-5) and transcription factor IRF3 37. Here, IRF3 is linked to infection.