Figure 1

Selective TLR7 signaling. Natural ligands of TLR7 include ssRNA, particularly viral particles (HCV). Once an HCV virion enters the hepatocyte, it engages the TLR7 receptor resulting in the formation of a complex facilitated by the recruitment of adapter protein, MyD88 and TIR, which occurs in the endosomal compartment. This complex then triggers a series of signal transduction pathways culminating in the formation of IRAK/IRF7/TRAF6 complex. IRF7 will translocate to the nucleus and transactivate the production of type I interferons (IFN-α and β). Exclusive TLR7 agonists generate activation of type I interferons, while TLR7/8 agonists result in the generation of proinflammatory cytokines, such as IL-2, IL-8, and TNF along with interferon α/β, which may result in development of undesirable adverse events. Hence, selective TLR7 agonists are ideal in the treatment of hepatitis viruses.