Toll-like receptors (TLRs) mediate the activation of immune cells and are important for the initiation of specific immune responses. Specifically, defective TLR signaling leads to impaired adaptive immune responses and delayed hepatitis B virus (HBV) clearance in the hydrodynamic injection mouse model. We found that TLR7 agonists could stimulate peripheral blood lymphocytes to produce potent antiviral cytokines in vitro and modulate adaptive immune responses to HBV in vivo. While TLR7 stimulated production of antiviral cytokines could effectively inhibit HBV replication, the HBV-specific T cells are possibly required for complete HBV clearance from the liver. In the present study, we will analyze the activation status of immune cells induced by TLR7 agonist in the mouse model and examine the consequences of the pre-activation of the host immune system for adaptive immunity. We also ask whether the interferons (IFNs) or other cytokines produced by PBMCs after TLR7 stimulation are the major mediators of potent HBV inhibition. Finally, we will study whether TLR7 as an IFN-stimulated gene (ISG) may be increasingly expressed by TLR7-mediated IFN production in a positively regulatory loop, thereby resulting in overshooting responses in the host.