Treatment of chronic hepatitis B with pattern recognition receptor agonists: Current status and potential for a cure

Hepatitis B virus (HBV) has been considered to be a “stealth virus” that induces negligible innate immune responses during the early phase of infection. However, recent studies with newly developed experimental systems have revealed that virus infection can be recognized by pattern recognition receptors (PRR), eliciting a cytokine response that controls the replication of the virus. The molecular mechanisms by which interferons and other inflammatory cytokines suppress HBV replication and modulate HBV cccDNA metabolism and function are just beginning to be revealed. In agreement with the notion that the developmental and functional status of intrahepatic innate immunity determines the activation and maturation of the HBV-specific adaptive immune response and thus the outcome of HBV infection, pharmacological activation of intrahepatic innate immune responses with TLR7/8/9 or STING agonists efficiently controls HBV infection in preclinical studies and thus holds great promise for the cure of chronic hepatitis B. This article forms part of a symposium in Antiviral Research on “An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B.”