Skip to main content
. 2008 Dec 19;227(1):87–94. doi: 10.1111/j.1600-065X.2008.00726.x

Figure 1.

Figure 1

 Cytoplasmic and endosomal sensors of viral nucleic acids. This figure illustrates the detection of viral products by retinoic acid‐inducible gene I (RIG‐I)‐like receptor (RLR) and Toll‐like receptor (TLR) family members. TLR3, TLR7/ 8, and TLR9 are located on endosomal compartments in which they sense their double‐stranded RNA (dsRNA), single‐stranded RNA (ssRNA), and CpG DNA ligands, respectively. TLR3 signals through the adapter protein Toll/interleukin‐1 (IL‐1) receptor (TIR) domain‐containing adapter‐inducing interferon‐β (TRIF), which activates tumor necrosis factor (TNF) receptor‐associated factor 3 (TRAF3) (not shown) and the TANK‐binding kinase 1 (TBK‐1) complex leading to interferon (IFN) regulatory factor 7 (IRF‐7) activation and IFN signaling. TRIF also signals through TRAF6, which leads to nuclear factor κB (NF‐κB) activation and inflammatory cytokine production. TLR7, TLR8, and TLR9 signal through the MyD88 adapter. MyD88 signals through a protein complex consisting of TRAF6 and IL‐1 receptor‐associated kinase 1/4 (IRAK1/4) (not shown), leading to the activation of type I IFN and NF‐κB signaling. RLR family members, melanoma differentiation‐associated gene 5 (MDA5), retinoic acid‐inducible gene I (RIG‐I), and laboratory of genetics and physiology‐2 (LGP2), are cytoplasmic proteins that detect viral products within the cytosol. MDA5 and RIG‐I signal through IFN‐β promoter stimulator 1 (IPS‐1), which is located on the mitochondrial membrane. IPS‐1 signals through TRAF3 and the TBK‐1/inhibitor of NF‐κB kinase ε complex to activate IRF‐3 and IRF‐7 and then type I IFN. IPS‐1 also signals through FAS‐associated death domain‐containing protein (FADD) leading to the activation of caspase‐8 and caspase‐10 (not shown), which causes NF‐κB activation and inflammatory cytokine production. LGP2 does not signal through IPS‐1 and is considered to be a negative regulator of RIG‐I.