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RIG-I-like receptor signaling pathway
RIG-I-like receptor signaling pathway
| MDA-5 | LGP2 | RIG-1 | AIM2 | TREX1 | DDX41 |
| DAI | IFI16 | cGAS | LRRFIP1 | TRIM56 | STING |
| TBK1 | IRF3 | TRIM25 | TRAF3 | TANK | NAP1 |
| SINTBAD | FADD | RIP1 | MAVS | IPS1 | NLRX1 |
| IKKε | DDX3 | TBK1I | NEMO | TRAF2/5/6 | Caspase-1 |
| NF-kB | IKKα | IKKβ |
Antiviral Innate Response
Antiviral innate responses are initiated by the cell following sensing of viral infection. The cell responds by producing antiviral cytokines and enzymes to shut down viral replication and enhance adaptive immune response.
RIG-I-like Receptors
RIG-I (retinoic acid-inducible gene I), MDA5 (melanoma differentiation associated factor 5), and LGP2 (laboratory of genetics and physiology 2) belong to the RIG-I-like receptor (RLR) family, which are involved in intracellular virus recognition. A discrepancy between RLR receptors and Toll-like Receptors (TLRs), is that TLRs identify extracellular viruses, whereas RLRs recognize viral DNA/RNA that has already entered the cell. The three receptors are DExD/H box helicases and exhibit high primary sequence conservation within their helicase domains. RLRs detect double-stranded (ds) viral DNA or RNA. The RIG-I and MDA5 proteins contain N-terminal CARD (Caspase Recruitment Domain) signaling domain, which when activated, lead to the triggering of the antiviral signaling pathway. While LGP2 contains an RNA binding domain, it does not contain a CARD-domain Instead, the protein negatively inhibits RIG-I and MDA5. Other suppressors of RIG-I/MDA5 include Dihydroxyacetone kinase (DAK), A20, ring-finger protein 125 (RNF125), suppressor of IKKε (SIKE), and peptidyl-propyl isomerase 1 (Pin1).
