Fig. 3.

Viral interference with accessory cellular components involved in PRR activation. MeV can interfere with RLR activation by targeting the phosphatase PP1 using 2 distinct mechanisms. MeV V protein can interact with PP1 to prevent the dephosphorylation of MDA-5 required for activation. MeV can interact on the cell surface with the C-lectin receptor DC-SIGN which results in the association of PP1-inhibitor 1 with PP1 thus preventing RLR dephosphorylation. Ebola virus VP35 protein, MERS-CoV 4a protein and arenavirus NP can interfere with PACT binding to dsRNA, a mechanism that potentiates RLR activation. RLR ubiquitination is also essential for adequate activation and transport to MAVS for subsequent IFN signaling events to take place. Riplet and TRIM25 are critical to RIG-I ubiquitination. IAV-NS1 and Denv sfRNA can interfere with TRIM25 activity, whereas Hepatitis C NS3-4A protease can cleave Riplet to impair RIG-I ubiquitination. The mitochondrial-targeting chaperone 14-3-3ε is responsible for RIG-I translocation to the mitochondrial membrane. DenV NS3 protein targets 14-3-3ε using a phosphomimetic domain that displaces activated RIG-I from this chaperone. WNV NS3 possesses a similar domain