Accumulating evidence shows that during viral infection, K63-linked ubiquitination by the E3 ligase tripartite motif containing 25 (TRIM25, also called estrogen-responsive finger protein) and Riplet (also called RING-finger protein [RNF135] or REUL) facilitates the association of RIG-I and mitochondrial antiviral-signaling protein (MAVS) promoting type I IFN induction. Here, MAVS is linked to viral infectious disease.