Two distinct signaling pathways activate the host innate immunity against viral infection. One pathway is reliant on members of the Toll-like receptor (TLR) family while the other uses the RNA helicase RIG-I as a receptor for intracellular viral double-stranded RNA as a trigger for the immune response. VISA is a mitochondrial membrane protein that was identified as a critical component in the IFN-b signaling pathways that recruits IRF-3 to RIG-I, leading to its activation and that of NF-κB. VISA is also thought to interact with other components of the innate immune pathway such as the TLR adapter protein TRIF, TRAF2 and TRAF6. VISA also interacts with the IKKα, IKKβ and IKKε kinases through its C-terminal region. Cleavage of this region by the Hepatitis C virus (HCV) protease allows HCV to escape the host immune system. At least three isoforms of VISA are known to exist.