Anti-RIG-I (aa1-211) monoclonal antibody, clone 2D4

The innate immune system is an important line of defense for the body against invasion by pathogens such as bacteria and viruses, and its key component is the recognition of pathogens. Pattern recognition receptors (PRRs) trigger a series of immune responses by recognizing structurally conserved pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), activating the relevant signaling pathways to clear pathogens. The retinoic acid-inducible gene I-like receptor family (RLRs) is an extremely important class of intracellular cytoplasmic viral RNA-recognizing receptors, mainly composed of retinoic acid-inducible gene-I (RIG-I), laboratory of genetics and physiology 2 (LGP2) and melanoma differentiation-associated gene 5 (MDA5), which initiates an antiviral immune response by activating the interferon signaling pathway.

RIG-I, also known as DDX58, was first identified during all-trans retinoic acid-induced differentiation of the acute promyelocytic leukemia cell line NB4. It has three highly conserved structural domains, including a pair of N-terminal tandem caspase activation and recruitment domains (CARDs), an atypical RNA-dependent ATPase motor domain, and a C-terminal RNA-binding domain. The C-terminal RNA-binding domain consists of approximately 170 amino acid residues and is primarily responsible for recognizing viral RNA. Since overexpression of this binding domain inhibits IFN expression induced by viral infection, this binding domain is also thought to play an inhibitory role, interacting with CARD and inhibiting RIG-I activation in the RIG-I resting state.

Figure 1. Structure-based model of RIG-I activation
(Source: Thoresen D, et al. 2021)

CARD is mainly responsible for the activation of downstream signaling pathways, and in the absence of viral infection, the CARD active region of RIG-I is closed by Hel2i and RIG-I is in a state of autoinhibition. During viral infection, RIG-I binds ATP and viral RNA, and conformational changes expose the CARD. At this point, TRIM25, which acts as an E3 ubiquitin ligase, can bind to RIG-I and induce tetramerization of RIG-I by covalent or non-covalent binding of K63-linked polyubiquitin chains to the lysine residue at position K172 in the CARD. Multimerized RIG-I transmits activation signals downstream through the interaction of its own CARD with the CARD of the mitochondrial antiviral signaling protein (MAVS), ultimately inducing the expression of pro-inflammatory cytokines and IFN-I, as well as the establishment of an intracellular antiviral state.

Anti-retinoic acid-inducible gene-I monoclonal antibody
Anti-DDX58 monoclonal antibody